neurology

Idiopathic Normal Pressure Hydrocephalus A Review

Nathan Hinkle — Wed, 16 Sep 2026 05:00:00 +0000

Date Added:

September 16, 2026

Journal/Publication:

JAMA

Publisher:

The American Medical Association

Publication Date:

September 14, 2026

URL:

E1-E14

Type:

Meta-analyses, Reviews, and Guidelines

CME Credits:

Format:

Article

DOI (1):

doi: 10.1001/jama.2026.15519

Keywords

Idiopathic Normal Pressure Hydrocephalus

neurology

cognitive assessment

MeSH

Hydrocephalus, Normal Pressure*

Cognitive Dysfunction* / therapy

urinary incontinence

RPR Commentary: A review of what we know about normal pressure hydrocephalus, and condition affecting up to 4% of older adults. James W. Mold, MPH.

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Abstract
Importance Idiopathic normal pressure hydrocephalus (iNPH) is a progressive neurological disorder characterized by cerebral ventricular enlargement that is typically associated with gait impairment and often urinary dysfunction and cognitive decline in older adults. iNPH prevalence is approximately 1% to 4% among individuals 65 years and older and 6% to 8% among those 80 years and older.

Observations iNPH is a multifactorial disorder involving interactions among cerebrospinal fluid (CSF) circulation, vascular dysfunction, and white matter injury. Unlike secondary NPH, iNPH occurs without a known antecedent event such as subarachnoid hemorrhage. Gait disturbance, including a broad-based, slow, shuffling gait and impaired turning, occurs in 85% to 95% of patients with iNPH and is often the earliest symptom. Urinary dysfunction occurs in approximately 75% to 90% of patients with iNPH and commonly includes urgency, nocturia, urge incontinence, or leakage. Cognitive impairment is reported in 60% to 80% of patients with iNPH, predominantly involving impaired attention, processing speed, working memory, verbal fluency, and cognitive flexibility. iNPH is diagnosed primarily based on characteristic clinical findings and neuroimaging (typically brain magnetic resonance imaging) demonstrating cerebral ventricular and subarachnoid space enlargement. Although necessary for diagnosis, these neuroimaging findings are not reliably associated with response to treatment. Early diagnosis of NPH is important because shorter symptom duration and less advanced disease are associated with more favorable outcomes. Patients being evaluated for iNPH should undergo large-volume lumbar puncture with removal of 30 to 50 mL of CSF to confirm the diagnosis and predict shunt responsiveness, measured as improvement in objective gait measures starting within hours after drainage. Extended lumbar drainage with removal of 200 to 300 mL of CSF over several days in an inpatient setting provides higher prognostic accuracy, and may be performed in patients with high clinical suspicion and a negative or equivocal clinical response to lumbar puncture. Treatment for iNPH is CSF diversion with shunt placement, most commonly performed with ventriculoperitoneal shunts, although ventriculoatrial and lumboperitoneal shunts may have similar efficacy. After shunting, approximately 75% to 80% of patients have gait velocity improvement; cognitive and urinary improvements occur in approximately 50% to 70%. Complications of shunts include overdrainage and underdrainage (10%-30%), presenting as postural headaches and subdural collections, and recurrence or worsening of iNPH symptoms, shunt malfunction (10%-20%), and shunt infections (<1%-2%).

Conclusions and Relevance iNPH affects approximately 1% to 4% of adults 65 years and older and is associated with gait impairment, cognitive decline, and urinary dysfunction. Symptoms improve in approximately 70% to 90% of patients with iNPH who undergo shunt surgery.

Author/s:

S. Farzad Maroufi, Sevil Yasar, Abhay Moghekar, Mark G. Luciano

Peripheral Neuropathy: A Review

Megan George — Wed, 19 Nov 2025 22:20:00 +0000

Date Added:

November 19, 2025

Journal/Publication:

JAMA

Publication Date:

November 17, 2025

URL:

Peripheral Neuropathy: A Review

Type:

Meta-analyses, Reviews, and Guidelines

Format:

Article

DOI (1):

doi: 10.1001/jama.2025.19400

Keywords

neurology

neuralgia

Peripheral Nerves

MeSH

antidepressive agents

antidepressive agents, tricyclic

Charcot-Marie-Tooth Disease

blood glucose

Cisplatin

diabetic neuropathies

duloxetine hydrochloride

gabapentin

Hypesthesia

hypotension

Hypotension, Orthostatic

Reverse Transcriptase Inhibitors

Venlafaxine Hydrochloride

Peripheral Nerves

neuralgia

A review of the causes and treatment of the symptoms of peripheral neuropathy. Figure 2 and Table 1 may be particularly helpful. James W. Mold, MD, MPH

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Importance Peripheral neuropathy, defined as damage to peripheral nerves, affects approximately 1% of adults worldwide. More than 200 causes of peripheral neuropathy exist, with symptoms ranging in severity from mild toe numbness to debilitating symptoms that can require a wheelchair. Diabetes is the most common cause of neuropathy, affecting approximately 206 million people worldwide.

Observations Peripheral neuropathy is typically length-dependent, which means that symptoms appear in the longest nerve axons (toes) and progress proximally over time. Peripheral neuropathy is typically symmetric and affects sensory axons more than motor axons. Diabetic neuropathy, which is often associated with both sensory symptoms, such as pain, tingling, or numbness; mild weakness; and autonomic symptoms, such as orthostatic hypotension, accounts for more than 50% of peripheral neuropathy in Western populations. Other causes of neuropathy include hereditary causes, such as Charcot-Marie-Tooth disease, toxic neuropathy from medications (chemotherapies [eg, cisplatin, paclitaxel, vincristine], amiodarone, or HIV nucleotide reverse transcriptase inhibitors [eg, stavudine, zalcitabine]); alcohol; vitamin deficiencies such as vitamin B12; and monoclonal gammopathies. Up to 27% of adults with neuropathy have no identifiable etiology for their neuropathy after diagnostic testing. Recommended initial testing includes blood glucose (for diabetes), serum B12 with metabolites (methylmalonic acid with or without homocysteine), and serum protein electrophoresis with immunofixation (for monoclonal gammopathies). First-line medications for neuropathic pain are the α2-δ calcium channel subunit ligands, such as gabapentin and pregabalin; serotonin norepinephrine reuptake inhibitors, such as duloxetine and venlafaxine; and tricyclic antidepressants, such as amitryptyline and nortriptyline. Pain often persists despite medical management. At least a 50% reduction in pain was observed in 38% of those with painful diabetic peripheral neuropathy receiving 1200 mg of gabapentin daily. Combination drug therapies for neuropathic pain may provide added benefit. The prognosis of peripheral neuropathy depends on its underlying cause, but complete reversal of nerve damage is uncommon even in cases for which there are available treatments.

Conclusions and Relevance Peripheral neuropathy affects approximately 1% of adults worldwide and may cause sensory, motor, and autonomic symptoms. Diabetes is the most common cause of peripheral neuropathy in Western countries. First-line therapies for neuropathic pain include gabapentin, pregabalin, duloxetine, and amitriptyline.

Author/s:

Michelle L. Mauermann, Nathan P. Staff

Cognitive Behavioral Therapy for Insomnia in People With Chronic Disease: A Systematic Review and Meta-Analysis

Megan George — Tue, 23 Sep 2025 14:04:10 +0000

Date Added:

September 23, 2025

Journal/Publication:

JAMA Internal Medicine

Publication Date:

September 22, 2025

URL:

Cognitive Behavioral Therapy for Insomnia in People With Chronic Disease: A Systematic Review and Meta-Analysis

Type:

Meta-analyses, Reviews, and Guidelines

Format:

Article

DOI (1):

10.1001/jamainternmed.2025.4610

Keywords

PMID (1):

40982264

MeSH

sleep

Adult

Humans

sleep initiation and maintenance disorders

chronic pain

Sleep Latency

quality of life

Irritable Bowel Syndrome

Neoplasms

stroke

chronic disease

Cognitive Behavioral Therapy

This systematic review/meta-analysis confirms the benefits of cognitive behavioral therapy for patients with insomnia in the face of chronic health challenges. James W. Mold, MD, MPH

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Importance: Insomnia is highly prevalent among individuals with chronic disease (eg, chronic pain, cardiovascular disease, and cancer) and results in poorer disease outcomes and quality of life. Cognitive behavioral therapy for insomnia (CBT-I) is recommended as first-line treatment for insomnia. However, concerns remain about its applicability and efficacy in people with chronic disease.

Objective: To evaluate the nature, efficacy, and acceptability of CBT-I in adults with chronic disease, and to identify moderators of treatment outcomes.

Data sources: Systematic searches were conducted in PsycINFO, Medline, Embase, and CENTRAL from database inception to June 5, 2025. Additional records were identified from reference lists of relevant reviews and studies.

Study selection: Eligible studies were randomized clinical trials (RCTs) involving adults (aged ≥18 years) with chronic disease and insomnia. Studies using CBT-I with measured sleep outcomes were included.

Data extraction and synthesis: Two assessors extracted data from RCTs. Hedges g was used to calculate effect sizes, and random effects meta-analyses were conducted. Heterogeneity was assessed via I2. Subgroup analyses examined whether outcomes varied by delivery format, chronic condition type, or control group.

Main outcomes and measures: Primary outcomes included insomnia severity, sleep efficiency, and sleep onset latency. Secondary outcomes included treatment acceptability and adverse effects.

Results: Sixty-seven RCTs (5232 participants) met inclusion criteria, including chronic diseases such as cancer, chronic pain, irritable bowel syndrome, and stroke. CBT-I was associated with significantly improved outcomes for insomnia severity (g = 0.98; 95% CI, 0.81-1.16) and moderate effect sizes regarding sleep efficiency (g = 0.77; 95% CI, 0.63-0.91) and sleep onset latency (g = 0.64; 95% CI, 0.50-0.78). Subgroup analyses revealed some sample, treatment, and methodological moderators (eg, longer treatment yielded better outcomes for sleep efficiency and sleep onset latency). Satisfaction with CBT-I was high, with a mean dropout rate of 13.3%. Treatment-related adverse effects were rare.

Conclusions and relevance: This systematic review and meta-analysis showed that CBT-I demonstrated strong efficacy and acceptability in chronic disease populations, with moderate to large effect sizes that appear comparable to those in non-chronic disease populations. Efficacy of CBT-I was similar across a range of disease subgroups. Future research should explore the role and nature of treatment adaptations for specific populations and increase access to CBT-I in medical settings.

Author/s:

Amelia J. Scott, Ashleigh B. Correa, Madelyne A. Bisby

Efficacy and Safety of Seltorexant in Insomnia Disorder: A Randomized Clinical Trial

Megan George — Tue, 02 Sep 2025 13:28:04 +0000

Date Added:

September 2, 2025

Journal/Publication:

JAMA Psychiatry

Publication Date:

August 13, 2025

URL:

Efficacy and Safety of Seltorexant in Insomnia Disorder: A Randomized Clinical Trial

Type:

Clinical Research Results

Format:

Article

DOI (1):

10.1001/jamapsychiatry.2025.1999

Keywords

sleep medicine

neurology

Psychiatry and Behavioral Health

Seltorexant

Insomnia medications

sleep disorders

PMID (1):

40802194

MeSH

sleep initiation and maintenance disorders

A randomized controlled trial of a new hypnotic on sleep initiation and maintenance. James W. Mold, MD, MPH

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Importance: Existing pharmacological treatments for insomnia have significant limitations.

Objective: To assess the effective dose range, safety, and tolerability of the novel selective orexin-2 receptor antagonist seltorexant in insomnia disorder.

Design, setting, and participants: This randomized, double-blind, active- and placebo-controlled, dose-finding, polysomnography study was conducted from November 2017 to April 2019 at 55 sites in 6 countries and analyzed in August 2019. The timeline for submission of this data for publication was impacted by internal strategic decision-making. Adults (aged 18-64 years) and older adults (aged 65-85 years) with insomnia (Insomnia Severity Index score ≥15) and no psychiatric comorbidity were included.

Interventions: Participants were randomized 1:1:1:1:1 to receive nightly oral-seltorexant (5 mg, 10 mg, or 20 mg), placebo, or zolpidem (5-10 mg) for 14 days.

Main outcomes and measures: Primary and key secondary outcomes included the dose-response relationship of night 1 latency to persistent sleep (LPS) and wake after sleep onset over the first 6 hours (WASO-6). Other secondary outcomes included night 13 LPS and WASO-6. Due to asymmetrical distributions of LPS and WASO-6 at baseline, log transformation was applied and results were expressed as back-transformed least-squares mean (LSM) ratios for comparisons between groups.

Results: Overall, 364 participants (mean [SD] age, 57.8 [12.4] years; 246 [67.6%] female) received seltorexant, 5 mg (n = 71), 10 mg (n = 74), or 20 mg (n = 71); placebo (n = 75); or zolpidem (n = 73). The night 1 dose-response relationship for LPS was significant (with trend test t statistics ≥3.99 and adjusted P values <.001 for all 4 prespecified models), with greater improvements in seltorexant, 10 mg and 20 mg, vs placebo (10 mg: LSM ratio, 0.64; 90% CI, 0.51-0.81; 20 mg: LSM ratio, 0.51; 90% CI, 0.41-0.64) and in seltorexant, 20 mg, vs zolpidem (LSM ratio, 0.71; 90% CI, 0.57-0.88). The night 1 dose-response relationship for WASO-6 was also significant, with trend test t statistics ≥3.99 and adjusted P values <.001 for all 4 prespecified models (seltorexant, 10 mg: LSM ratio, 0.68; 90% CI, 0.55-0.85; seltorexant, 20 mg: LSM ratio, 0.60; 90% CI, 0.48-0.74). Night 1 LPS and WASO-6 improvements were maintained on night 13 for seltorexant, 10 mg and 20 mg, but diminished for zolpidem. On night 13, compared with zolpidem, seltorexant, 10 mg and 20 mg, improved LPS by 30% and 28%, respectively, and seltorexant, 20 mg, improved WASO-6 by 31%. Treatment-emergent adverse events (TEAEs) were lower across the combined seltorexant doses (73/216 [33.8%]) relative to placebo (37/75 [49.3%]) and zolpidem (31/73 [42.5%]). Two participants experienced serious TEAEs during the double-blind phase (1 in the seltorexant, 20 mg, group and 1 in the zolpidem group). Three participants in the seltorexant, 5 mg, and 1 in the seltorexant, 20 mg, group experienced asymptomatic electrocardiogram-related TEAEs leading to discontinuation.

Conclusions and relevance: Among participants with insomnia in this study, seltorexant, 10 mg and 20 mg, improved sleep initiation and maintenance throughout 14 days of treatment. Seltorexant was generally well tolerated.

Trial registration: ClinicalTrials.gov Identifier: NCT03375203.

Author/s:

Sofie Mesens, Andrew D Krystal, Rama Melkote, Haiyan Xu, Gahan Pandina, Jay B Saoud, Remy Luthringer, Adam Savitz, Wayne C Drevets

Understanding and Managing Headaches in Children and Teens

Megan George — Tue, 05 Aug 2025 14:39:21 +0000

Date Added:

August 5, 2025

Journal/Publication:

JAMA Pediatrics

Publication Date:

August 1, 2025

URL:

Understanding and Managing Headaches in Children and Teens

Type:

Patient Education Materials

Format:

Article

DOI (1):

10.1001/jamapediatrics.2025.1111

Keywords

headache

neurology

pediatric

PMID (1):

40549366

MeSH

headache

tension-type headache

Information for parents about headaches in children. James W. Mold, MD, MPH

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This JAMA Pediatrics Patient Page discusses symptoms and treatment of headaches in children and teens.

Author/s:

Cynthia-Mae M Hunt, Lindsay A Thompson

Frontotemporal dementia

Erin Blanchette — Wed, 13 Dec 2023 17:01:01 +0000

Date Added:

December 13, 2023

Journal/Publication:

Canadian Medical Association Journal

Publisher:

Canadian Medical Association

Publication Date:

December 10, 2023

Issue:

Volume:

195

Pages:

E1660

URL:

Frontotemporal dementia

Type:

Meta-analyses, Reviews, and Guidelines

Format:

Article

DOI (1):

10.1503/cmaj.230407

Keywords

Frontotemporal Dementia

neurology

dementia

Alzheimer Disease

PMID (1):

38081627

MeSH

Frontotemporal Dementia

alzheimer disease

Pick Disease of the Brain

Cognition

brain

Temporal Lobe

Behavioral Symptoms/diagnosis

Magnetic Resonance Imaging

A concise review of fronto-temporal dementia. James W. Mold, MD, MPH

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Frontotemporal dementia should be considered in adults aged 50–75 years presenting with behavioural or language changes. After Alzheimer disease, it is the second most common cause of dementia among adults younger than 65 years.1 Frontal and temporal lobe degeneration results in behavioural or language impairment.

Author/s:

Raul Medina-Rioja, Gina Gonzalez-Calderon, Mario Masellis

Normal pressure hydrocephalus treated with ventriculoperitoneal shunt

Aubrey Delammermore — Sat, 28 Jan 2023 06:00:00 +0000

Date Added:

January 28, 2023

Journal/Publication:

CMAJ

Publisher:

CMA Impact

Publication Date:

January 23, 2023

Issue:

Volume:

195

Pages:

E115-E119

URL:

Normal pressure hydrocephalus treated with ventriculoperitoneal shunt

Type:

Meta-analyses, Reviews, and Guidelines

Format:

Article

DOI (1):

10.1503/cmaj.221027

Keywords

ventriculoperitoneal shunt

PMID (1):

36690362

MeSH

Hydrocephalus* / surgery

Hydrocephalus, Normal Pressure*

retrospective studies

treatment outcome

ventriculoperitoneal shunt

A concise review of what we know about normal pressure hydrocephalus. James W. Mold, MD, MPH

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Normal pressure hydrocephalus is a form of adult hydrocephalus with ventriculomegaly in the absence of any structural blockage of the cerebrospinal fluid circulation.

Normal pressure hydrocephalus is a partially reversible cause of dementia, manifesting with a triad of cognitive impairment, gait disturbance and urinary incontinence.

A detailed cognitive assessment, neurologic examination and brain imaging is necessary to exclude alternative causes and confirm the diagnosis.

High-volume lumbar puncture with pre- and postprocedure gait assessment is recommended as a confirmatory test before a decision is made regarding therapeutic interventions such as shunting.

Author/s:

Fereshtehnejad, S., Nicholls, M., Huang, S., Akter, R.

Review of systemic and syndromic complications of cannabis use: A review

Aubrey Delammermore — Mon, 19 Dec 2022 06:00:00 +0000

Date Added:

December 19, 2022

Journal/Publication:

Medicine

Publisher:

Wolters Kluwer Health

Publication Date:

December 9, 2022

Issue:

Volume:

101

Pages:

e32111

URL:

Review of systemic and syndromic complications of cannabis use: A review

Type:

Meta-analyses, Reviews, and Guidelines

Format:

Article

DOI (1):

10.1097/MD.0000000000032111

Keywords

complications of cannabis use

MeSH

A review of some of the complications of cannabis abuse. James W. Mold, MD, MPH

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Purpose of review: Prescribed and non-prescribed cannabis use is common. Providers in specialties treating chronic pain – primary care, pain management, and neurology–will be coming across medical cannabis as a treatment for chronic pain, regardless of whether they are prescribers. It is important to be aware of the systemic and syndromic complications of acute and chronic cannabis use in the differential diagnosis of cardiac, cardiovascular, cerebrovascular, gastrointestinal, and psychiatric disorders.

Recent Findings: Medical cannabis is legal in 36 states. Studies have shown several potentially serious adverse effects associated with cannabis use.

Summary: Cannabis use has the potential to cause several complications that can be easily overlooked without a preexisting high index of suspicion.

Author/s:

Shah, J., Fermo, O.