Literature Review

Using the NeuroPace RNS system to monitor long-term epileptic-like activity, researchers have confirmed that there is a uniform circadian pattern to this brain activity. Studying 134 subjects, Spencer et al found the epileptiform activity peaked during normal sleeping hours. They also discovered a monophasic, nocturnally dominant rhythm in the neocortical areas of the brain and a more complex pattern, with a diurnal peak, in limbic sections of the brain.  Some volunteers were also found to have a dual oscillator pattern to the brain activity, displaying a circadian and ultradian pattern.

Spencer D, Sun F, Brown S, Jobst, B, Wong V, Mirro E et al. Circadian and ultradian patterns of epileptiform discharges differ by seizure-onset location during long-term ambulatory intracranial monitoring. Epilepsia. 2016;57(9):1495-1502.

Using the NeuroPace RNS system to monitor long-term epileptic-like activity, researchers have confirmed that there is a uniform circadian pattern to this brain activity. Studying 134 subjects, Spencer et al found the epileptiform activity peaked during normal sleeping hours. They also discovered a monophasic, nocturnally dominant rhythm in the neocortical areas of the brain and a more complex pattern, with a diurnal peak, in limbic sections of the brain.  Some volunteers were also found to have a dual oscillator pattern to the brain activity, displaying a circadian and ultradian pattern.

Spencer D, Sun F, Brown S, Jobst, B, Wong V, Mirro E et al. Circadian and ultradian patterns of epileptiform discharges differ by seizure-onset location during long-term ambulatory intracranial monitoring. Epilepsia. 2016;57(9):1495-1502.

Using the NeuroPace RNS system to monitor long-term epileptic-like activity, researchers have confirmed that there is a uniform circadian pattern to this brain activity. Studying 134 subjects, Spencer et al found the epileptiform activity peaked during normal sleeping hours. They also discovered a monophasic, nocturnally dominant rhythm in the neocortical areas of the brain and a more complex pattern, with a diurnal peak, in limbic sections of the brain.  Some volunteers were also found to have a dual oscillator pattern to the brain activity, displaying a circadian and ultradian pattern.

Spencer D, Sun F, Brown S, Jobst, B, Wong V, Mirro E et al. Circadian and ultradian patterns of epileptiform discharges differ by seizure-onset location during long-term ambulatory intracranial monitoring. Epilepsia. 2016;57(9):1495-1502.

Patients with tuberous sclerosis complex (TSC) are at higher than average risk of developing epilepsy if they exhibit several systemic disease manifestations, according to a recent analysis of the TSC Natural History Database. After factoring out confounding variables like age, gender, and TSC mutation, Anna Jeong and Michael Wong of Washington University School of Medicine found that cardiac rhabdomyomas, retinal hamartomas, renal cysts, renal angiomyolipomas, shagreen patches, and facial angiofibromas increased the likelihood of TSC patients developing epilepsy.

Jeong A, Wong M. Systemic disease manifestations associated with epilepsy in tuberous sclerosis complex. Epilepsia. 2016;57(9):1443-1449.

Patients with tuberous sclerosis complex (TSC) are at higher than average risk of developing epilepsy if they exhibit several systemic disease manifestations, according to a recent analysis of the TSC Natural History Database. After factoring out confounding variables like age, gender, and TSC mutation, Anna Jeong and Michael Wong of Washington University School of Medicine found that cardiac rhabdomyomas, retinal hamartomas, renal cysts, renal angiomyolipomas, shagreen patches, and facial angiofibromas increased the likelihood of TSC patients developing epilepsy.

Jeong A, Wong M. Systemic disease manifestations associated with epilepsy in tuberous sclerosis complex. Epilepsia. 2016;57(9):1443-1449.

Patients with tuberous sclerosis complex (TSC) are at higher than average risk of developing epilepsy if they exhibit several systemic disease manifestations, according to a recent analysis of the TSC Natural History Database. After factoring out confounding variables like age, gender, and TSC mutation, Anna Jeong and Michael Wong of Washington University School of Medicine found that cardiac rhabdomyomas, retinal hamartomas, renal cysts, renal angiomyolipomas, shagreen patches, and facial angiofibromas increased the likelihood of TSC patients developing epilepsy.

Jeong A, Wong M. Systemic disease manifestations associated with epilepsy in tuberous sclerosis complex. Epilepsia. 2016;57(9):1443-1449.

Performing resting state functioning MRIs can help distinguish temporal lobe epilepsy that’s accompanied by mesial temporal sclerosis (TLE-MTS) from temporal lobe epilepsy without the sclerosis. That conclusion was dreached by researchers who compared 34 TLE patients to 34 controls who were matched for age and gender and in whom the presence of mesial temporal sclerosis was definitively established by means of histologic examination of surgical tissue. More specifically, the investigators found that the fractional amplitude of low-frequency fluctuations (fALFF) in the blood oxygen level-dependent resting state fMRI was reduced in the ipsilateral amygdala and hippocampus among TLE patients with mesial temporal sclerosis. By contrast, among TLE patients without sclerosis, there was only marginally reduced fALFF in the ipsilateral amygdala but none in the hippocampus. 

Reyes A, Thesen D, Wang X, Hahn D, Yoo D, Kuzniecky R et al.  Resting-state functional MRI distinguishes temporal lobe epilepsy subtypes. Epilepsia. 2016;57(9):1475-1484.  

Performing resting state functioning MRIs can help distinguish temporal lobe epilepsy that’s accompanied by mesial temporal sclerosis (TLE-MTS) from temporal lobe epilepsy without the sclerosis. That conclusion was dreached by researchers who compared 34 TLE patients to 34 controls who were matched for age and gender and in whom the presence of mesial temporal sclerosis was definitively established by means of histologic examination of surgical tissue. More specifically, the investigators found that the fractional amplitude of low-frequency fluctuations (fALFF) in the blood oxygen level-dependent resting state fMRI was reduced in the ipsilateral amygdala and hippocampus among TLE patients with mesial temporal sclerosis. By contrast, among TLE patients without sclerosis, there was only marginally reduced fALFF in the ipsilateral amygdala but none in the hippocampus. 

Reyes A, Thesen D, Wang X, Hahn D, Yoo D, Kuzniecky R et al.  Resting-state functional MRI distinguishes temporal lobe epilepsy subtypes. Epilepsia. 2016;57(9):1475-1484.  

Performing resting state functioning MRIs can help distinguish temporal lobe epilepsy that’s accompanied by mesial temporal sclerosis (TLE-MTS) from temporal lobe epilepsy without the sclerosis. That conclusion was dreached by researchers who compared 34 TLE patients to 34 controls who were matched for age and gender and in whom the presence of mesial temporal sclerosis was definitively established by means of histologic examination of surgical tissue. More specifically, the investigators found that the fractional amplitude of low-frequency fluctuations (fALFF) in the blood oxygen level-dependent resting state fMRI was reduced in the ipsilateral amygdala and hippocampus among TLE patients with mesial temporal sclerosis. By contrast, among TLE patients without sclerosis, there was only marginally reduced fALFF in the ipsilateral amygdala but none in the hippocampus. 

Reyes A, Thesen D, Wang X, Hahn D, Yoo D, Kuzniecky R et al.  Resting-state functional MRI distinguishes temporal lobe epilepsy subtypes. Epilepsia. 2016;57(9):1475-1484.  

Clinical Question: What are current recommendations for diagnosis, management, and prevention of acute gastrointestinal infection in immune-competent adults?

Background: Acute diarrheal infection is a leading cause of healthcare visits and lost quality of life. The Centers for Disease Control and Prevention estimates there are 47.8 million cases annually, with a healthcare economy burden of $150 million.

Study Design: American College of Gastroenterology (ACG) practice guideline.

Setting: Expert panel.

Synopsis: Stool diagnostic studies may be used for dysentery with moderate-severe disease and symptoms lasting more than seven days (strong recommendation, low level of evidence). Traditional diagnostic methods in most cases fail to reveal etiology (strong recommendation, low level of evidence). Treatment with probiotics or prebiotics is not recommended (strong recommendation, moderate level of evidence). Bismuth subsalicylates may be considered for prophylaxis against traveler’s diarrhea (strong recommendation, high level of evidence). Short-term antibiotic chemoprophylaxis also may be considered for high-risk groups (strong recommendation, high level of evidence). Empiric antimicrobial therapy is not recommended except in cases of traveler’s diarrhea (strong recommendation, high level of evidence). Loperamide may be used as an adjunct to antibiotics for traveler’s diarrhea (strong recommendation, moderate level of evidence).

Bottom Line: ACG acute diarrheal illness guidelines have been updated. Few recommendations are strong, and very few have high levels of evidence.

Citation: Riddle MS, DuPont HL, Conner BA. ACG clinical guideline: diagnosis, treatment, and prevention of acute diarrheal infections in adults. Am J Gastroenterol. 2016;111(5):602-622.

Clinical Question: What are current recommendations for diagnosis, management, and prevention of acute gastrointestinal infection in immune-competent adults?

Background: Acute diarrheal infection is a leading cause of healthcare visits and lost quality of life. The Centers for Disease Control and Prevention estimates there are 47.8 million cases annually, with a healthcare economy burden of $150 million.

Study Design: American College of Gastroenterology (ACG) practice guideline.

Setting: Expert panel.

Synopsis: Stool diagnostic studies may be used for dysentery with moderate-severe disease and symptoms lasting more than seven days (strong recommendation, low level of evidence). Traditional diagnostic methods in most cases fail to reveal etiology (strong recommendation, low level of evidence). Treatment with probiotics or prebiotics is not recommended (strong recommendation, moderate level of evidence). Bismuth subsalicylates may be considered for prophylaxis against traveler’s diarrhea (strong recommendation, high level of evidence). Short-term antibiotic chemoprophylaxis also may be considered for high-risk groups (strong recommendation, high level of evidence). Empiric antimicrobial therapy is not recommended except in cases of traveler’s diarrhea (strong recommendation, high level of evidence). Loperamide may be used as an adjunct to antibiotics for traveler’s diarrhea (strong recommendation, moderate level of evidence).

Bottom Line: ACG acute diarrheal illness guidelines have been updated. Few recommendations are strong, and very few have high levels of evidence.

Citation: Riddle MS, DuPont HL, Conner BA. ACG clinical guideline: diagnosis, treatment, and prevention of acute diarrheal infections in adults. Am J Gastroenterol. 2016;111(5):602-622.

Clinical Question: What are current recommendations for diagnosis, management, and prevention of acute gastrointestinal infection in immune-competent adults?

Background: Acute diarrheal infection is a leading cause of healthcare visits and lost quality of life. The Centers for Disease Control and Prevention estimates there are 47.8 million cases annually, with a healthcare economy burden of $150 million.

Study Design: American College of Gastroenterology (ACG) practice guideline.

Setting: Expert panel.

Synopsis: Stool diagnostic studies may be used for dysentery with moderate-severe disease and symptoms lasting more than seven days (strong recommendation, low level of evidence). Traditional diagnostic methods in most cases fail to reveal etiology (strong recommendation, low level of evidence). Treatment with probiotics or prebiotics is not recommended (strong recommendation, moderate level of evidence). Bismuth subsalicylates may be considered for prophylaxis against traveler’s diarrhea (strong recommendation, high level of evidence). Short-term antibiotic chemoprophylaxis also may be considered for high-risk groups (strong recommendation, high level of evidence). Empiric antimicrobial therapy is not recommended except in cases of traveler’s diarrhea (strong recommendation, high level of evidence). Loperamide may be used as an adjunct to antibiotics for traveler’s diarrhea (strong recommendation, moderate level of evidence).

Bottom Line: ACG acute diarrheal illness guidelines have been updated. Few recommendations are strong, and very few have high levels of evidence.

Citation: Riddle MS, DuPont HL, Conner BA. ACG clinical guideline: diagnosis, treatment, and prevention of acute diarrheal infections in adults. Am J Gastroenterol. 2016;111(5):602-622.

Clinical Question: Do risk-assessment models (RAMs) accurately predict which hospitalized medical patients are at risk for venous thromboembolism (VTE)?

Background: Predicting which patients are at high risk for VTE is important. Several models exist, but limited data support their generalizability and accuracy in medical inpatients.

Study Design: Retrospective cohort.

Setting: Hospitals participating in the Michigan Hospital Medicine Safety Consortium (MHMSC).

Synopsis: Data collected through MHMSC for selected medical patients were used in the Kucher, Padua, predictive IMPROVE, and Intermountain DVT risk-assessment models. Patients were classified as “low risk” or “at risk” based on each RAM. Follow-up data came from chart extraction (100% of patients) and 90-day post-discharge telephone calls (58% of patients). The primary outcome was image-confirmed hospital associated VTE, including proximal upper- or proximal lower-extremity DVT or pulmonary embolism. These RAMs classified less than 20% of patients as “at risk.” The incidence of VTE was less than 1%. In this external validation study, the Kucher RAM was the least discriminate and the Intermountain was the best, but none yielded results equivalent to the original studies.

This study was limited by the retrospective design, subjectivity of some risk factors (such as immobility), and inability to obtain 90-day telephone follow-up in all patients. Lastly, the binary approach (“at risk” versus “low risk”) may not align with the original derivation studies in which each factor was evaluated independently.

Bottom Line: The incidence of VTE is low in medical inpatients, and current RAMs may not accurately identify at-risk patients.

Citation: Greene MT, Spyropoulos AC, Chopra V, et al. Validation of risk assessment models of venous thromboembolism in hospitalized medical patients. Am J Med. 2016;129(9):1001.e9-1001.e18. doi:10.1016/j.amjmed.2016.03.031.

Clinical Question: Do risk-assessment models (RAMs) accurately predict which hospitalized medical patients are at risk for venous thromboembolism (VTE)?

Background: Predicting which patients are at high risk for VTE is important. Several models exist, but limited data support their generalizability and accuracy in medical inpatients.

Study Design: Retrospective cohort.

Setting: Hospitals participating in the Michigan Hospital Medicine Safety Consortium (MHMSC).

Synopsis: Data collected through MHMSC for selected medical patients were used in the Kucher, Padua, predictive IMPROVE, and Intermountain DVT risk-assessment models. Patients were classified as “low risk” or “at risk” based on each RAM. Follow-up data came from chart extraction (100% of patients) and 90-day post-discharge telephone calls (58% of patients). The primary outcome was image-confirmed hospital associated VTE, including proximal upper- or proximal lower-extremity DVT or pulmonary embolism. These RAMs classified less than 20% of patients as “at risk.” The incidence of VTE was less than 1%. In this external validation study, the Kucher RAM was the least discriminate and the Intermountain was the best, but none yielded results equivalent to the original studies.

This study was limited by the retrospective design, subjectivity of some risk factors (such as immobility), and inability to obtain 90-day telephone follow-up in all patients. Lastly, the binary approach (“at risk” versus “low risk”) may not align with the original derivation studies in which each factor was evaluated independently.

Bottom Line: The incidence of VTE is low in medical inpatients, and current RAMs may not accurately identify at-risk patients.

Citation: Greene MT, Spyropoulos AC, Chopra V, et al. Validation of risk assessment models of venous thromboembolism in hospitalized medical patients. Am J Med. 2016;129(9):1001.e9-1001.e18. doi:10.1016/j.amjmed.2016.03.031.

Clinical Question: Do risk-assessment models (RAMs) accurately predict which hospitalized medical patients are at risk for venous thromboembolism (VTE)?

Background: Predicting which patients are at high risk for VTE is important. Several models exist, but limited data support their generalizability and accuracy in medical inpatients.

Study Design: Retrospective cohort.

Setting: Hospitals participating in the Michigan Hospital Medicine Safety Consortium (MHMSC).

Synopsis: Data collected through MHMSC for selected medical patients were used in the Kucher, Padua, predictive IMPROVE, and Intermountain DVT risk-assessment models. Patients were classified as “low risk” or “at risk” based on each RAM. Follow-up data came from chart extraction (100% of patients) and 90-day post-discharge telephone calls (58% of patients). The primary outcome was image-confirmed hospital associated VTE, including proximal upper- or proximal lower-extremity DVT or pulmonary embolism. These RAMs classified less than 20% of patients as “at risk.” The incidence of VTE was less than 1%. In this external validation study, the Kucher RAM was the least discriminate and the Intermountain was the best, but none yielded results equivalent to the original studies.

This study was limited by the retrospective design, subjectivity of some risk factors (such as immobility), and inability to obtain 90-day telephone follow-up in all patients. Lastly, the binary approach (“at risk” versus “low risk”) may not align with the original derivation studies in which each factor was evaluated independently.

Bottom Line: The incidence of VTE is low in medical inpatients, and current RAMs may not accurately identify at-risk patients.

Citation: Greene MT, Spyropoulos AC, Chopra V, et al. Validation of risk assessment models of venous thromboembolism in hospitalized medical patients. Am J Med. 2016;129(9):1001.e9-1001.e18. doi:10.1016/j.amjmed.2016.03.031.

Clinical Question: How common are neurologic findings in acute HIV infection?

Background: The incidence of neurologic findings with acute HIV is unknown.

Study Design: Cohort study.

Setting: Bangkok, Thailand.

Synopsis: In this study, 134 patients were identified after presenting for voluntary HIV testing. Five others were enrolled through an ongoing local study. All 139 participants underwent structured neurologic evaluations at enrollment (median of 19 days after presumed exposure), then at four and 12 weeks. Combination antiretroviral therapy (cART) was initiated immediately after initial evaluation.

The cohort was 93% male. Mean age was younger than 30 years. Fifty-three percent of participants experienced some neurologic finding within 12 weeks of diagnosis. One-third (33%) were cognitive symptoms, predominantly problems of concentration (24% of patients) and memory (16% of patients). One-third (34%) were motor findings, and 11% were neuropathy. Forty-nine percent of the neurologic issues were present at diagnosis. Symptoms were mostly mild, although one patient developed fulminant Guillain-Barré syndrome. Patients with neurologic findings had higher viral loads at diagnosis (mean plasma log10 HIV RNA 5.9 versus 5.4; P = 0.006). Participants with and without neurologic findings had similar cerebral spinal fluid viral loads (mean log10 HIV RNA 3.7 versus 3.1, P = 0.14) and serum CD4 counts (339 versus 381 cells/mm3; P = 0.46). Neurologic findings resolved within one month of cART treatment in 90% of patients. Study limitations include lack of a control cohort and potential confounding from illicit drug use among participants.

Bottom Line: Acute HIV infection commonly causes mild neurologic problems, which remit with treatment.

Citation: Hellmuth J, Fletcher JL, Valcour V, et al. Neurologic signs and symptoms frequently manifest in acute HIV infection. Neurology. 2016;87(2):148-154.

Clinical Question: How common are neurologic findings in acute HIV infection?

Background: The incidence of neurologic findings with acute HIV is unknown.

Study Design: Cohort study.

Setting: Bangkok, Thailand.

Synopsis: In this study, 134 patients were identified after presenting for voluntary HIV testing. Five others were enrolled through an ongoing local study. All 139 participants underwent structured neurologic evaluations at enrollment (median of 19 days after presumed exposure), then at four and 12 weeks. Combination antiretroviral therapy (cART) was initiated immediately after initial evaluation.

The cohort was 93% male. Mean age was younger than 30 years. Fifty-three percent of participants experienced some neurologic finding within 12 weeks of diagnosis. One-third (33%) were cognitive symptoms, predominantly problems of concentration (24% of patients) and memory (16% of patients). One-third (34%) were motor findings, and 11% were neuropathy. Forty-nine percent of the neurologic issues were present at diagnosis. Symptoms were mostly mild, although one patient developed fulminant Guillain-Barré syndrome. Patients with neurologic findings had higher viral loads at diagnosis (mean plasma log10 HIV RNA 5.9 versus 5.4; P = 0.006). Participants with and without neurologic findings had similar cerebral spinal fluid viral loads (mean log10 HIV RNA 3.7 versus 3.1, P = 0.14) and serum CD4 counts (339 versus 381 cells/mm3; P = 0.46). Neurologic findings resolved within one month of cART treatment in 90% of patients. Study limitations include lack of a control cohort and potential confounding from illicit drug use among participants.

Bottom Line: Acute HIV infection commonly causes mild neurologic problems, which remit with treatment.

Citation: Hellmuth J, Fletcher JL, Valcour V, et al. Neurologic signs and symptoms frequently manifest in acute HIV infection. Neurology. 2016;87(2):148-154.

Clinical Question: How common are neurologic findings in acute HIV infection?

Background: The incidence of neurologic findings with acute HIV is unknown.

Study Design: Cohort study.

Setting: Bangkok, Thailand.

Synopsis: In this study, 134 patients were identified after presenting for voluntary HIV testing. Five others were enrolled through an ongoing local study. All 139 participants underwent structured neurologic evaluations at enrollment (median of 19 days after presumed exposure), then at four and 12 weeks. Combination antiretroviral therapy (cART) was initiated immediately after initial evaluation.

The cohort was 93% male. Mean age was younger than 30 years. Fifty-three percent of participants experienced some neurologic finding within 12 weeks of diagnosis. One-third (33%) were cognitive symptoms, predominantly problems of concentration (24% of patients) and memory (16% of patients). One-third (34%) were motor findings, and 11% were neuropathy. Forty-nine percent of the neurologic issues were present at diagnosis. Symptoms were mostly mild, although one patient developed fulminant Guillain-Barré syndrome. Patients with neurologic findings had higher viral loads at diagnosis (mean plasma log10 HIV RNA 5.9 versus 5.4; P = 0.006). Participants with and without neurologic findings had similar cerebral spinal fluid viral loads (mean log10 HIV RNA 3.7 versus 3.1, P = 0.14) and serum CD4 counts (339 versus 381 cells/mm3; P = 0.46). Neurologic findings resolved within one month of cART treatment in 90% of patients. Study limitations include lack of a control cohort and potential confounding from illicit drug use among participants.

Bottom Line: Acute HIV infection commonly causes mild neurologic problems, which remit with treatment.

Citation: Hellmuth J, Fletcher JL, Valcour V, et al. Neurologic signs and symptoms frequently manifest in acute HIV infection. Neurology. 2016;87(2):148-154.

Clinical Question: Is the 10-point cognitive screener (10-CS) effective in screening for delirium in older adults with hip fracture?

Background: Delirium in elderly hip fracture patients has been established as a significant comorbidity. There is, however, no agreement on the most appropriate and practical screening tool. Commonly used screening methods, which focus on the detection of cognitive impairment as a surrogate, are time-consuming, insensitive for mild impairment, and limited in their application to patients with impaired dexterity and poor education.

Study Design: Prospective cohort study.

Setting: Tertiary referral hospital in São Paulo, Brazil.

Synopsis: In the study, 147 consecutive hip fracture patients over age 60 were screened using the 10-CS. This test stratifies patients into three categories: normal, possible, and probable cognitive impairment. Development of in-hospital delirium was evaluated by daily Confusion Assessment Method testing administered by a geriatrician. Patients categorized as probable cognitive impairment were more likely to develop delirium (hazard ratio, 7.48; 95% CI, 2.2–25.4).

Hospitalists involved in perioperative care should consider using this simple screening tool. With an area under ROC curve of 0.83 (95% CI, 0.76–0.89), it effectively detects delirium in this high-risk population. Independently, patients who developed delirium had a longer length of stay (median 11.0 versus 7.0; P < 0.001). This serves as a reminder of the importance of screening and preventing delirium in this population.

Bottom Line: The 10-CS tool is practical in its application and effective in identifying elderly hip fracture patients at risk for delirium.

Citation: Fortes-Filho SQ, Apolinario D, Melo JA, Suzuki I, Sitta MD, Garcez-Leme LE. Predicting delirium after hip fracture with a 2-min cognitive screen: prospective cohort study [published online ahead of print May 17, 2016]. Age Ageing. pii:afw084.

Clinical Question: Is the 10-point cognitive screener (10-CS) effective in screening for delirium in older adults with hip fracture?

Background: Delirium in elderly hip fracture patients has been established as a significant comorbidity. There is, however, no agreement on the most appropriate and practical screening tool. Commonly used screening methods, which focus on the detection of cognitive impairment as a surrogate, are time-consuming, insensitive for mild impairment, and limited in their application to patients with impaired dexterity and poor education.

Study Design: Prospective cohort study.

Setting: Tertiary referral hospital in São Paulo, Brazil.

Synopsis: In the study, 147 consecutive hip fracture patients over age 60 were screened using the 10-CS. This test stratifies patients into three categories: normal, possible, and probable cognitive impairment. Development of in-hospital delirium was evaluated by daily Confusion Assessment Method testing administered by a geriatrician. Patients categorized as probable cognitive impairment were more likely to develop delirium (hazard ratio, 7.48; 95% CI, 2.2–25.4).

Hospitalists involved in perioperative care should consider using this simple screening tool. With an area under ROC curve of 0.83 (95% CI, 0.76–0.89), it effectively detects delirium in this high-risk population. Independently, patients who developed delirium had a longer length of stay (median 11.0 versus 7.0; P < 0.001). This serves as a reminder of the importance of screening and preventing delirium in this population.

Bottom Line: The 10-CS tool is practical in its application and effective in identifying elderly hip fracture patients at risk for delirium.

Citation: Fortes-Filho SQ, Apolinario D, Melo JA, Suzuki I, Sitta MD, Garcez-Leme LE. Predicting delirium after hip fracture with a 2-min cognitive screen: prospective cohort study [published online ahead of print May 17, 2016]. Age Ageing. pii:afw084.

Clinical Question: Is the 10-point cognitive screener (10-CS) effective in screening for delirium in older adults with hip fracture?

Background: Delirium in elderly hip fracture patients has been established as a significant comorbidity. There is, however, no agreement on the most appropriate and practical screening tool. Commonly used screening methods, which focus on the detection of cognitive impairment as a surrogate, are time-consuming, insensitive for mild impairment, and limited in their application to patients with impaired dexterity and poor education.

Study Design: Prospective cohort study.

Setting: Tertiary referral hospital in São Paulo, Brazil.

Synopsis: In the study, 147 consecutive hip fracture patients over age 60 were screened using the 10-CS. This test stratifies patients into three categories: normal, possible, and probable cognitive impairment. Development of in-hospital delirium was evaluated by daily Confusion Assessment Method testing administered by a geriatrician. Patients categorized as probable cognitive impairment were more likely to develop delirium (hazard ratio, 7.48; 95% CI, 2.2–25.4).

Hospitalists involved in perioperative care should consider using this simple screening tool. With an area under ROC curve of 0.83 (95% CI, 0.76–0.89), it effectively detects delirium in this high-risk population. Independently, patients who developed delirium had a longer length of stay (median 11.0 versus 7.0; P < 0.001). This serves as a reminder of the importance of screening and preventing delirium in this population.

Bottom Line: The 10-CS tool is practical in its application and effective in identifying elderly hip fracture patients at risk for delirium.

Citation: Fortes-Filho SQ, Apolinario D, Melo JA, Suzuki I, Sitta MD, Garcez-Leme LE. Predicting delirium after hip fracture with a 2-min cognitive screen: prospective cohort study [published online ahead of print May 17, 2016]. Age Ageing. pii:afw084.

Self-administration of an inhalable formulation of levodopa rapidly improves motor function and significantly reduces off time in people with Parkinson’s disease, according to data published in the September issue of Movement Disorders. The drug may fill an unmet need for a well-tolerated and noninvasive intervention, according to the authors.

Over time, many patients with Parkinson’s disease lose a predictable and sustained response to levodopa. Irregular intestinal absorption of oral levodopa formulations may be one cause of this reduced response. Among currently available therapies, apomorphine acts rapidly and effectively aborts off episodes. The drug is ineffective if taken orally, however, and subcutaneous injection often requires premedication with an antiemetic.

CVT-301 is an inhalable formulation of levodopa designed for pulmonary absorption. The drug is administered using a passive, breath-actuated delivery system and it improved motor function in a phase IIa dose-finding study. Peter A. LeWitt, MD, MMSc, a neurologist at Henry Ford West Bloomfield Hospital in Michigan, and colleagues conducted a phase IIb trial to evaluate the efficacy and safety of self-administered CVT-301 among patients with Parkinson’s disease in a clinical setting and at home during off episodes.

Investigators Evaluated Two Doses

Dr. LeWitt’s group conducted a randomized, double-blind, controlled trial that lasted for four weeks. Eligible participants were between ages 30 and 80, had typical clinical features of Parkinson’s disease, took oral levodopa at least four times daily, and had predictable off episodes totaling two or more hours per day. People with a history of chronic respiratory disease within the previous five years or a Mini-Mental State Examination score lower than 25 were excluded.

After learning how to use the inhaler system, patients were randomized to CVT-301 or placebo (an inhalation-grade lactose monohydrate) for four weeks to treat as many as three off episodes per day. During the first two weeks, the dose of CVT-301 was 35 mg. During the second two weeks, the dose of CVT-301 was 50 mg, and the dose of placebo was increased.

The researchers assessed participants with the Unified Parkinson’s Disease Rating Scale (UPDRS) Part III at screening and at the end of weeks 1, 2, and 4. During the latter three visits, investigators blinded to treatment assignments obtained UPDRS Part III scores for the predose off state and at 10, 20, 30, and 60 minutes post dose. Patients were rated subjectively as achieving or not achieving an on state during the 60-minute observation period. Patients also responded to the Patient Global Impression of Change scale at the end of weeks 2 and 4.

Drug Improved Motor Scores

Dr. LeWitt and colleagues enrolled 89 patients in the study. Of these participants, 86 used at least one dose of study drug, and 75 completed the study. Average age was approximately 62, and participants had received a diagnosis of Parkinson’s disease an average of nine years before study initiation. Mean off time was approximately six hours per day.

As measured in clinic by UPDRS Part III score, motor function improved significantly during off episodes after administration of CVT-301. At the end of week 1, the least-squares mean change in UPDRS Part III score was –9.9 points for 35 mg of CVT-301, compared with –5.3 points for placebo. One week later, the mean change was –10.2 points for the first 50-mg dose of CVT-301, compared with –3.5 points for placebo. At the end of week 4, the mean change was –10.0 points for 50 mg of CVT-301 versus –3.1 points for placebo.

Post hoc analyses indicated that onset of action was evident at 10 minutes for both doses of CVT-301. The mean improvement in motor scores remained significant versus placebo through the 60-minute final assessment. At 60 minutes, the week 4 treatment effect (ie, 50 mg vs placebo) exceeded the week 1 treatment effect (ie, 35 mg vs placebo) by 4.3 points.

Approximately 47% of the active group and 33% of the placebo group reported treatment-emergent adverse events. Adverse events with an incidence of 5.0% or greater in the CVT-301 group were dizziness, cough, and nausea, each of which was reported in three patients. Dyskinesia was reported in one patient in each treatment group. Two patients, both in the placebo group, experienced severe adverse events: drop attack and dyskinesia.

Results May Reflect Treatment Duration

Inhaled CVT-301 “provided rapid amelioration of off episodes,” said Dr. LeWitt. “The average improvement in motor function was similar for both dose levels. However, the average difference from placebo was numerically greater after the 50-mg dose, at least partly because of a decrease in placebo response in weeks 2 and 4, compared with week 1.” The average improvement associated with active treatment greatly exceeded the reported minimum values for a clinically relevant change in Part III scores, he added.

Cough is a particular concern for inhaled drugs, but all reported instances of cough were mild, and none led to dose reduction or discontinuation. No patient reported dyspnea, wheezing, or bronchospasm.

A potential limitation of the study is that patients were not allowed to take the study drug more than three times daily, even though they had an average reported baseline frequency of 3.6 off episodes per day. In addition, the study assessed 35- and 50-mg doses of CVT-301 as sequential treatments. Overall differences between the doses thus might reflect treatment duration rather than dose strength. Nevertheless, “the study’s findings support continued investigation of CVT-301 for rapid treatment of off episodes,” Dr. LeWitt concluded.

—Erik Greb

Suggested Reading

LeWitt PA, Hauser RA, Grosset DG, et al. A randomized trial of inhaled levodopa (CVT-301) for motor fluctuations in Parkinson’s disease. Mov Disord. 2016;31(9):1356-1365.

Self-administration of an inhalable formulation of levodopa rapidly improves motor function and significantly reduces off time in people with Parkinson’s disease, according to data published in the September issue of Movement Disorders. The drug may fill an unmet need for a well-tolerated and noninvasive intervention, according to the authors.

Over time, many patients with Parkinson’s disease lose a predictable and sustained response to levodopa. Irregular intestinal absorption of oral levodopa formulations may be one cause of this reduced response. Among currently available therapies, apomorphine acts rapidly and effectively aborts off episodes. The drug is ineffective if taken orally, however, and subcutaneous injection often requires premedication with an antiemetic.

CVT-301 is an inhalable formulation of levodopa designed for pulmonary absorption. The drug is administered using a passive, breath-actuated delivery system and it improved motor function in a phase IIa dose-finding study. Peter A. LeWitt, MD, MMSc, a neurologist at Henry Ford West Bloomfield Hospital in Michigan, and colleagues conducted a phase IIb trial to evaluate the efficacy and safety of self-administered CVT-301 among patients with Parkinson’s disease in a clinical setting and at home during off episodes.

Investigators Evaluated Two Doses

Dr. LeWitt’s group conducted a randomized, double-blind, controlled trial that lasted for four weeks. Eligible participants were between ages 30 and 80, had typical clinical features of Parkinson’s disease, took oral levodopa at least four times daily, and had predictable off episodes totaling two or more hours per day. People with a history of chronic respiratory disease within the previous five years or a Mini-Mental State Examination score lower than 25 were excluded.

After learning how to use the inhaler system, patients were randomized to CVT-301 or placebo (an inhalation-grade lactose monohydrate) for four weeks to treat as many as three off episodes per day. During the first two weeks, the dose of CVT-301 was 35 mg. During the second two weeks, the dose of CVT-301 was 50 mg, and the dose of placebo was increased.

The researchers assessed participants with the Unified Parkinson’s Disease Rating Scale (UPDRS) Part III at screening and at the end of weeks 1, 2, and 4. During the latter three visits, investigators blinded to treatment assignments obtained UPDRS Part III scores for the predose off state and at 10, 20, 30, and 60 minutes post dose. Patients were rated subjectively as achieving or not achieving an on state during the 60-minute observation period. Patients also responded to the Patient Global Impression of Change scale at the end of weeks 2 and 4.

Drug Improved Motor Scores

Dr. LeWitt and colleagues enrolled 89 patients in the study. Of these participants, 86 used at least one dose of study drug, and 75 completed the study. Average age was approximately 62, and participants had received a diagnosis of Parkinson’s disease an average of nine years before study initiation. Mean off time was approximately six hours per day.

As measured in clinic by UPDRS Part III score, motor function improved significantly during off episodes after administration of CVT-301. At the end of week 1, the least-squares mean change in UPDRS Part III score was –9.9 points for 35 mg of CVT-301, compared with –5.3 points for placebo. One week later, the mean change was –10.2 points for the first 50-mg dose of CVT-301, compared with –3.5 points for placebo. At the end of week 4, the mean change was –10.0 points for 50 mg of CVT-301 versus –3.1 points for placebo.

Post hoc analyses indicated that onset of action was evident at 10 minutes for both doses of CVT-301. The mean improvement in motor scores remained significant versus placebo through the 60-minute final assessment. At 60 minutes, the week 4 treatment effect (ie, 50 mg vs placebo) exceeded the week 1 treatment effect (ie, 35 mg vs placebo) by 4.3 points.

Approximately 47% of the active group and 33% of the placebo group reported treatment-emergent adverse events. Adverse events with an incidence of 5.0% or greater in the CVT-301 group were dizziness, cough, and nausea, each of which was reported in three patients. Dyskinesia was reported in one patient in each treatment group. Two patients, both in the placebo group, experienced severe adverse events: drop attack and dyskinesia.

Results May Reflect Treatment Duration

Inhaled CVT-301 “provided rapid amelioration of off episodes,” said Dr. LeWitt. “The average improvement in motor function was similar for both dose levels. However, the average difference from placebo was numerically greater after the 50-mg dose, at least partly because of a decrease in placebo response in weeks 2 and 4, compared with week 1.” The average improvement associated with active treatment greatly exceeded the reported minimum values for a clinically relevant change in Part III scores, he added.

Cough is a particular concern for inhaled drugs, but all reported instances of cough were mild, and none led to dose reduction or discontinuation. No patient reported dyspnea, wheezing, or bronchospasm.

A potential limitation of the study is that patients were not allowed to take the study drug more than three times daily, even though they had an average reported baseline frequency of 3.6 off episodes per day. In addition, the study assessed 35- and 50-mg doses of CVT-301 as sequential treatments. Overall differences between the doses thus might reflect treatment duration rather than dose strength. Nevertheless, “the study’s findings support continued investigation of CVT-301 for rapid treatment of off episodes,” Dr. LeWitt concluded.

—Erik Greb

Suggested Reading

LeWitt PA, Hauser RA, Grosset DG, et al. A randomized trial of inhaled levodopa (CVT-301) for motor fluctuations in Parkinson’s disease. Mov Disord. 2016;31(9):1356-1365.

Self-administration of an inhalable formulation of levodopa rapidly improves motor function and significantly reduces off time in people with Parkinson’s disease, according to data published in the September issue of Movement Disorders. The drug may fill an unmet need for a well-tolerated and noninvasive intervention, according to the authors.

Over time, many patients with Parkinson’s disease lose a predictable and sustained response to levodopa. Irregular intestinal absorption of oral levodopa formulations may be one cause of this reduced response. Among currently available therapies, apomorphine acts rapidly and effectively aborts off episodes. The drug is ineffective if taken orally, however, and subcutaneous injection often requires premedication with an antiemetic.

CVT-301 is an inhalable formulation of levodopa designed for pulmonary absorption. The drug is administered using a passive, breath-actuated delivery system and it improved motor function in a phase IIa dose-finding study. Peter A. LeWitt, MD, MMSc, a neurologist at Henry Ford West Bloomfield Hospital in Michigan, and colleagues conducted a phase IIb trial to evaluate the efficacy and safety of self-administered CVT-301 among patients with Parkinson’s disease in a clinical setting and at home during off episodes.

Investigators Evaluated Two Doses

Dr. LeWitt’s group conducted a randomized, double-blind, controlled trial that lasted for four weeks. Eligible participants were between ages 30 and 80, had typical clinical features of Parkinson’s disease, took oral levodopa at least four times daily, and had predictable off episodes totaling two or more hours per day. People with a history of chronic respiratory disease within the previous five years or a Mini-Mental State Examination score lower than 25 were excluded.

After learning how to use the inhaler system, patients were randomized to CVT-301 or placebo (an inhalation-grade lactose monohydrate) for four weeks to treat as many as three off episodes per day. During the first two weeks, the dose of CVT-301 was 35 mg. During the second two weeks, the dose of CVT-301 was 50 mg, and the dose of placebo was increased.

The researchers assessed participants with the Unified Parkinson’s Disease Rating Scale (UPDRS) Part III at screening and at the end of weeks 1, 2, and 4. During the latter three visits, investigators blinded to treatment assignments obtained UPDRS Part III scores for the predose off state and at 10, 20, 30, and 60 minutes post dose. Patients were rated subjectively as achieving or not achieving an on state during the 60-minute observation period. Patients also responded to the Patient Global Impression of Change scale at the end of weeks 2 and 4.

Drug Improved Motor Scores

Dr. LeWitt and colleagues enrolled 89 patients in the study. Of these participants, 86 used at least one dose of study drug, and 75 completed the study. Average age was approximately 62, and participants had received a diagnosis of Parkinson’s disease an average of nine years before study initiation. Mean off time was approximately six hours per day.

As measured in clinic by UPDRS Part III score, motor function improved significantly during off episodes after administration of CVT-301. At the end of week 1, the least-squares mean change in UPDRS Part III score was –9.9 points for 35 mg of CVT-301, compared with –5.3 points for placebo. One week later, the mean change was –10.2 points for the first 50-mg dose of CVT-301, compared with –3.5 points for placebo. At the end of week 4, the mean change was –10.0 points for 50 mg of CVT-301 versus –3.1 points for placebo.

Post hoc analyses indicated that onset of action was evident at 10 minutes for both doses of CVT-301. The mean improvement in motor scores remained significant versus placebo through the 60-minute final assessment. At 60 minutes, the week 4 treatment effect (ie, 50 mg vs placebo) exceeded the week 1 treatment effect (ie, 35 mg vs placebo) by 4.3 points.

Approximately 47% of the active group and 33% of the placebo group reported treatment-emergent adverse events. Adverse events with an incidence of 5.0% or greater in the CVT-301 group were dizziness, cough, and nausea, each of which was reported in three patients. Dyskinesia was reported in one patient in each treatment group. Two patients, both in the placebo group, experienced severe adverse events: drop attack and dyskinesia.

Results May Reflect Treatment Duration

Inhaled CVT-301 “provided rapid amelioration of off episodes,” said Dr. LeWitt. “The average improvement in motor function was similar for both dose levels. However, the average difference from placebo was numerically greater after the 50-mg dose, at least partly because of a decrease in placebo response in weeks 2 and 4, compared with week 1.” The average improvement associated with active treatment greatly exceeded the reported minimum values for a clinically relevant change in Part III scores, he added.

Cough is a particular concern for inhaled drugs, but all reported instances of cough were mild, and none led to dose reduction or discontinuation. No patient reported dyspnea, wheezing, or bronchospasm.

A potential limitation of the study is that patients were not allowed to take the study drug more than three times daily, even though they had an average reported baseline frequency of 3.6 off episodes per day. In addition, the study assessed 35- and 50-mg doses of CVT-301 as sequential treatments. Overall differences between the doses thus might reflect treatment duration rather than dose strength. Nevertheless, “the study’s findings support continued investigation of CVT-301 for rapid treatment of off episodes,” Dr. LeWitt concluded.

—Erik Greb

Suggested Reading

LeWitt PA, Hauser RA, Grosset DG, et al. A randomized trial of inhaled levodopa (CVT-301) for motor fluctuations in Parkinson’s disease. Mov Disord. 2016;31(9):1356-1365.

A new way to track the progression of Parkinson’s disease could help evaluate experimental treatments aimed at slowing or stopping the disease’s progression. “We provide evidence using task-based functional MRI (fMRI) for cortical and striatal functional deterioration in Parkinson’s disease over a one-year period,” researchers reported in the August 16 issue of Neurology.

Study results also describe unique patterns of functional changes in patients with multiple system atrophy (MSA) and progressive supranuclear palsy (PSP) that are more widespread, compared with those in Parkinson’s disease, suggesting that distinctive rates of disease progression in parkinsonian disorders may assist in future clinical studies of disease-modifying therapies.

While current treatments focus on controlling symptoms, biomarkers provide a quantifiable way to measure how medications address not just symptoms, but the neurologic changes behind them. Previous studies have used imaging techniques that require the injection of a drug that crosses the blood–brain barrier. “Our technique does not rely upon the injection of a drug. Not only is it noninvasive, it is much less expensive,” said senior study author David Vaillancourt, PhD, a Professor in the Department of Applied Physiology and Kinesiology at the University of Florida, Gainesville.

A total of 112 individuals were scanned at baseline and at one year while preforming a unimanual grip force task. The study cohort included 46 patients with Parkinson’s disease, 13 patients with MSA, 19 patients with PSP, and 34 healthy controls. The outcome measure was percent signal change in the prespecified brain regions.

A year after the baseline study, the 46 patients with Parkinson’s disease showed declining function in the primary motor cortex and putamen, compared with controls. Changes after one year in patients with MSA were exclusively extrastriatal and included a reduction in functional activity in the primary motor cortex, supplementary motor area, and superior cerebellum. In patients with PSP, all regions of interest were less active at one year, compared with baseline. Functional activity of the brain regions in the control group did not change during the study.

“Collectively, these findings point to disease-specific noninvasive progression markers of sensorimotor brain regions in parkinsonian disorders,” the researchers said.

The present findings build on two 2015 studies that used fMRI to document progressive deterioration from Parkinson’s disease, MSA, and PSP.

Suggested Reading

Burciu RG, Chung JW, Shukla P, et al. Functional MRI of disease progression in Parkinson disease and atypical parksonian syndromes. Neurology. 2016;87(7):709-717.

Burciu RG, Ofori E, Shukla P, et al. Distinct patters of brain activity in progressive supranuclear palsy and Parkinson’s disease. Mov Disord. 2015;30(9):1248-1258.

Oh M, Kim JS, Kim JY, et al. Subregional patterns of preferential striatal dopamine transporter loss differ in Parkinson disease, progressive supranuclear palsy, and multiple system atrophy. J Nucl Med. 2012;53(3):399-406.

Planetta PJ, Kurani AS, Shukla P, et al. Distinct functional and macrostructural brain changes in Parkinson’s disease and multiple system atrophy. Human Brain Mapp. 2015;36(3):1165-1179.

A new way to track the progression of Parkinson’s disease could help evaluate experimental treatments aimed at slowing or stopping the disease’s progression. “We provide evidence using task-based functional MRI (fMRI) for cortical and striatal functional deterioration in Parkinson’s disease over a one-year period,” researchers reported in the August 16 issue of Neurology.

Study results also describe unique patterns of functional changes in patients with multiple system atrophy (MSA) and progressive supranuclear palsy (PSP) that are more widespread, compared with those in Parkinson’s disease, suggesting that distinctive rates of disease progression in parkinsonian disorders may assist in future clinical studies of disease-modifying therapies.

While current treatments focus on controlling symptoms, biomarkers provide a quantifiable way to measure how medications address not just symptoms, but the neurologic changes behind them. Previous studies have used imaging techniques that require the injection of a drug that crosses the blood–brain barrier. “Our technique does not rely upon the injection of a drug. Not only is it noninvasive, it is much less expensive,” said senior study author David Vaillancourt, PhD, a Professor in the Department of Applied Physiology and Kinesiology at the University of Florida, Gainesville.

A total of 112 individuals were scanned at baseline and at one year while preforming a unimanual grip force task. The study cohort included 46 patients with Parkinson’s disease, 13 patients with MSA, 19 patients with PSP, and 34 healthy controls. The outcome measure was percent signal change in the prespecified brain regions.

A year after the baseline study, the 46 patients with Parkinson’s disease showed declining function in the primary motor cortex and putamen, compared with controls. Changes after one year in patients with MSA were exclusively extrastriatal and included a reduction in functional activity in the primary motor cortex, supplementary motor area, and superior cerebellum. In patients with PSP, all regions of interest were less active at one year, compared with baseline. Functional activity of the brain regions in the control group did not change during the study.

“Collectively, these findings point to disease-specific noninvasive progression markers of sensorimotor brain regions in parkinsonian disorders,” the researchers said.

The present findings build on two 2015 studies that used fMRI to document progressive deterioration from Parkinson’s disease, MSA, and PSP.

Suggested Reading

Burciu RG, Chung JW, Shukla P, et al. Functional MRI of disease progression in Parkinson disease and atypical parksonian syndromes. Neurology. 2016;87(7):709-717.

Burciu RG, Ofori E, Shukla P, et al. Distinct patters of brain activity in progressive supranuclear palsy and Parkinson’s disease. Mov Disord. 2015;30(9):1248-1258.

Oh M, Kim JS, Kim JY, et al. Subregional patterns of preferential striatal dopamine transporter loss differ in Parkinson disease, progressive supranuclear palsy, and multiple system atrophy. J Nucl Med. 2012;53(3):399-406.

Planetta PJ, Kurani AS, Shukla P, et al. Distinct functional and macrostructural brain changes in Parkinson’s disease and multiple system atrophy. Human Brain Mapp. 2015;36(3):1165-1179.

A new way to track the progression of Parkinson’s disease could help evaluate experimental treatments aimed at slowing or stopping the disease’s progression. “We provide evidence using task-based functional MRI (fMRI) for cortical and striatal functional deterioration in Parkinson’s disease over a one-year period,” researchers reported in the August 16 issue of Neurology.

Study results also describe unique patterns of functional changes in patients with multiple system atrophy (MSA) and progressive supranuclear palsy (PSP) that are more widespread, compared with those in Parkinson’s disease, suggesting that distinctive rates of disease progression in parkinsonian disorders may assist in future clinical studies of disease-modifying therapies.

While current treatments focus on controlling symptoms, biomarkers provide a quantifiable way to measure how medications address not just symptoms, but the neurologic changes behind them. Previous studies have used imaging techniques that require the injection of a drug that crosses the blood–brain barrier. “Our technique does not rely upon the injection of a drug. Not only is it noninvasive, it is much less expensive,” said senior study author David Vaillancourt, PhD, a Professor in the Department of Applied Physiology and Kinesiology at the University of Florida, Gainesville.

A total of 112 individuals were scanned at baseline and at one year while preforming a unimanual grip force task. The study cohort included 46 patients with Parkinson’s disease, 13 patients with MSA, 19 patients with PSP, and 34 healthy controls. The outcome measure was percent signal change in the prespecified brain regions.

A year after the baseline study, the 46 patients with Parkinson’s disease showed declining function in the primary motor cortex and putamen, compared with controls. Changes after one year in patients with MSA were exclusively extrastriatal and included a reduction in functional activity in the primary motor cortex, supplementary motor area, and superior cerebellum. In patients with PSP, all regions of interest were less active at one year, compared with baseline. Functional activity of the brain regions in the control group did not change during the study.

“Collectively, these findings point to disease-specific noninvasive progression markers of sensorimotor brain regions in parkinsonian disorders,” the researchers said.

The present findings build on two 2015 studies that used fMRI to document progressive deterioration from Parkinson’s disease, MSA, and PSP.

Suggested Reading

Burciu RG, Chung JW, Shukla P, et al. Functional MRI of disease progression in Parkinson disease and atypical parksonian syndromes. Neurology. 2016;87(7):709-717.

Burciu RG, Ofori E, Shukla P, et al. Distinct patters of brain activity in progressive supranuclear palsy and Parkinson’s disease. Mov Disord. 2015;30(9):1248-1258.

Oh M, Kim JS, Kim JY, et al. Subregional patterns of preferential striatal dopamine transporter loss differ in Parkinson disease, progressive supranuclear palsy, and multiple system atrophy. J Nucl Med. 2012;53(3):399-406.

Planetta PJ, Kurani AS, Shukla P, et al. Distinct functional and macrostructural brain changes in Parkinson’s disease and multiple system atrophy. Human Brain Mapp. 2015;36(3):1165-1179.

MRI-guided focused ultrasound thalamotomy reduces hand tremor in patients with essential tremor, according to data published August 25 in the New England Journal of Medicine. The technique also reduces disability and improves self-reported quality of life, said the researchers.

“We are excited to have this new noninvasive treatment option for patients who struggle every day with this debilitating neurologic disorder,” said Howard M. Eisenberg, MD, the R.K. Thompson Professor and Chair of Neurosurgery at the University of Maryland School of Medicine in Baltimore and an author of the study. “We saw an impressive reduction in tremors in hands and arms and an improvement in quality of life in patients who experienced no relief from medication.”

Dr. Eisenberg and colleagues randomized 76 patients with moderate to severe essential tremor that had not responded to at least two trials of medical therapy to unilateral focused ultrasound thalamotomy or a sham procedure. The investigators administered the Clinical Rating Scale for Tremor (CRST) and the Quality of Life in Essential Tremor (QUEST) questionnaire to participants at baseline and at one, three, six, and 12 months. Videotaped tremor assessments were rated by an independent group of neurologists who were blinded to the treatment assignments. After three months, patients in the sham-procedure group were allowed to cross over to active treatment.

The study’s primary outcome was the between-group difference in the change from baseline to three months in hand tremor, rated on Parts A and B of the CRST. Secondary outcomes included functional limitations in daily activities, measured according to eight items in the disability subsection of the CRST; quality of life, assessed with the QUEST at three months; and the durability of the reduction in hand tremor at 12 months.

Hand-tremor scores improved by 8.5 points in the intervention group and by 0.2 points among controls. Improvement occurred in the hand contralateral to the thalamotomy. The between-group difference in the mean change was 8.3 points. The improvement in the thalamotomy group was maintained at 12 months (change from baseline, 7.2 points). Focused ultrasound thalamotomy also improved total disability score by 62% at three months, compared with 3% among controls, and the improvement was sustained at 12 months. Patients’ self-rated quality of life improved by 46% at three months in the intervention group and by 3% among controls.

Adverse events of thalamotomy included gait disturbance (36% of patients) and paresthesias or numbness (38% of patients). These adverse events persisted at 12 months in 9% and 14% of patients, respectively.

In an accompanying editorial, Elan D. Louis, MD, Chief of the Division of Movement Disorders at Yale University in New Haven, Connecticut, said that the study results are promising, particularly since the procedure, unlike traditional thalamotomy, does not require entering the skull with a probe. “Nevertheless,” he added, “there are several important concerns.” The first concern is the limited follow-up period. The sustained benefit beyond one year is not known. “This is particularly important because of tachyphylaxis, which is the second concern,” Dr. Louis wrote. Tremor score in the group that underwent focused ultrasound thalamotomy increased from 8.84 at one month to 10.89 at 12 months, an increase of 23%. A third concern is that the procedure did not achieve large improvements in everyone; the percentage change in tremor was less than 20% in nine of 56 patients. “Even with these concerns,” Dr. Louis said, “the procedure will take its place among other surgical procedures for medically refractory essential tremor.”

—Erik Greb and Glenn Williams

Suggested Reading

Elias WJ, Lipsman N, Ondo WG, et al. A randomized trial of focused ultrasound thalamotomy for essential tremor. N Engl J Med. 2016;375(8):730-739.

Louis ED. Treatment of medically refractory essential tremor. N Engl J Med. 2016;375(8):792-793.

MRI-guided focused ultrasound thalamotomy reduces hand tremor in patients with essential tremor, according to data published August 25 in the New England Journal of Medicine. The technique also reduces disability and improves self-reported quality of life, said the researchers.

“We are excited to have this new noninvasive treatment option for patients who struggle every day with this debilitating neurologic disorder,” said Howard M. Eisenberg, MD, the R.K. Thompson Professor and Chair of Neurosurgery at the University of Maryland School of Medicine in Baltimore and an author of the study. “We saw an impressive reduction in tremors in hands and arms and an improvement in quality of life in patients who experienced no relief from medication.”

Dr. Eisenberg and colleagues randomized 76 patients with moderate to severe essential tremor that had not responded to at least two trials of medical therapy to unilateral focused ultrasound thalamotomy or a sham procedure. The investigators administered the Clinical Rating Scale for Tremor (CRST) and the Quality of Life in Essential Tremor (QUEST) questionnaire to participants at baseline and at one, three, six, and 12 months. Videotaped tremor assessments were rated by an independent group of neurologists who were blinded to the treatment assignments. After three months, patients in the sham-procedure group were allowed to cross over to active treatment.

The study’s primary outcome was the between-group difference in the change from baseline to three months in hand tremor, rated on Parts A and B of the CRST. Secondary outcomes included functional limitations in daily activities, measured according to eight items in the disability subsection of the CRST; quality of life, assessed with the QUEST at three months; and the durability of the reduction in hand tremor at 12 months.

Hand-tremor scores improved by 8.5 points in the intervention group and by 0.2 points among controls. Improvement occurred in the hand contralateral to the thalamotomy. The between-group difference in the mean change was 8.3 points. The improvement in the thalamotomy group was maintained at 12 months (change from baseline, 7.2 points). Focused ultrasound thalamotomy also improved total disability score by 62% at three months, compared with 3% among controls, and the improvement was sustained at 12 months. Patients’ self-rated quality of life improved by 46% at three months in the intervention group and by 3% among controls.

Adverse events of thalamotomy included gait disturbance (36% of patients) and paresthesias or numbness (38% of patients). These adverse events persisted at 12 months in 9% and 14% of patients, respectively.

In an accompanying editorial, Elan D. Louis, MD, Chief of the Division of Movement Disorders at Yale University in New Haven, Connecticut, said that the study results are promising, particularly since the procedure, unlike traditional thalamotomy, does not require entering the skull with a probe. “Nevertheless,” he added, “there are several important concerns.” The first concern is the limited follow-up period. The sustained benefit beyond one year is not known. “This is particularly important because of tachyphylaxis, which is the second concern,” Dr. Louis wrote. Tremor score in the group that underwent focused ultrasound thalamotomy increased from 8.84 at one month to 10.89 at 12 months, an increase of 23%. A third concern is that the procedure did not achieve large improvements in everyone; the percentage change in tremor was less than 20% in nine of 56 patients. “Even with these concerns,” Dr. Louis said, “the procedure will take its place among other surgical procedures for medically refractory essential tremor.”

—Erik Greb and Glenn Williams

Suggested Reading

Elias WJ, Lipsman N, Ondo WG, et al. A randomized trial of focused ultrasound thalamotomy for essential tremor. N Engl J Med. 2016;375(8):730-739.

Louis ED. Treatment of medically refractory essential tremor. N Engl J Med. 2016;375(8):792-793.

MRI-guided focused ultrasound thalamotomy reduces hand tremor in patients with essential tremor, according to data published August 25 in the New England Journal of Medicine. The technique also reduces disability and improves self-reported quality of life, said the researchers.

“We are excited to have this new noninvasive treatment option for patients who struggle every day with this debilitating neurologic disorder,” said Howard M. Eisenberg, MD, the R.K. Thompson Professor and Chair of Neurosurgery at the University of Maryland School of Medicine in Baltimore and an author of the study. “We saw an impressive reduction in tremors in hands and arms and an improvement in quality of life in patients who experienced no relief from medication.”

Dr. Eisenberg and colleagues randomized 76 patients with moderate to severe essential tremor that had not responded to at least two trials of medical therapy to unilateral focused ultrasound thalamotomy or a sham procedure. The investigators administered the Clinical Rating Scale for Tremor (CRST) and the Quality of Life in Essential Tremor (QUEST) questionnaire to participants at baseline and at one, three, six, and 12 months. Videotaped tremor assessments were rated by an independent group of neurologists who were blinded to the treatment assignments. After three months, patients in the sham-procedure group were allowed to cross over to active treatment.

The study’s primary outcome was the between-group difference in the change from baseline to three months in hand tremor, rated on Parts A and B of the CRST. Secondary outcomes included functional limitations in daily activities, measured according to eight items in the disability subsection of the CRST; quality of life, assessed with the QUEST at three months; and the durability of the reduction in hand tremor at 12 months.

Hand-tremor scores improved by 8.5 points in the intervention group and by 0.2 points among controls. Improvement occurred in the hand contralateral to the thalamotomy. The between-group difference in the mean change was 8.3 points. The improvement in the thalamotomy group was maintained at 12 months (change from baseline, 7.2 points). Focused ultrasound thalamotomy also improved total disability score by 62% at three months, compared with 3% among controls, and the improvement was sustained at 12 months. Patients’ self-rated quality of life improved by 46% at three months in the intervention group and by 3% among controls.

Adverse events of thalamotomy included gait disturbance (36% of patients) and paresthesias or numbness (38% of patients). These adverse events persisted at 12 months in 9% and 14% of patients, respectively.

In an accompanying editorial, Elan D. Louis, MD, Chief of the Division of Movement Disorders at Yale University in New Haven, Connecticut, said that the study results are promising, particularly since the procedure, unlike traditional thalamotomy, does not require entering the skull with a probe. “Nevertheless,” he added, “there are several important concerns.” The first concern is the limited follow-up period. The sustained benefit beyond one year is not known. “This is particularly important because of tachyphylaxis, which is the second concern,” Dr. Louis wrote. Tremor score in the group that underwent focused ultrasound thalamotomy increased from 8.84 at one month to 10.89 at 12 months, an increase of 23%. A third concern is that the procedure did not achieve large improvements in everyone; the percentage change in tremor was less than 20% in nine of 56 patients. “Even with these concerns,” Dr. Louis said, “the procedure will take its place among other surgical procedures for medically refractory essential tremor.”

—Erik Greb and Glenn Williams

Suggested Reading

Elias WJ, Lipsman N, Ondo WG, et al. A randomized trial of focused ultrasound thalamotomy for essential tremor. N Engl J Med. 2016;375(8):730-739.

Louis ED. Treatment of medically refractory essential tremor. N Engl J Med. 2016;375(8):792-793.