Medications for daytime sleepiness in individuals with idiopathic hypersomnia.

BACKGROUND: Idiopathic hypersomnia is a disorder of excessive daytime sleepiness, often accompanied by long sleep times or pronounced difficulty in awakening, in the absence of a known cause. The optimal treatment strategy for idiopathic hypersomnia is currently unknown. OBJECTIVES: To assess the effects of medications for daytime sleepiness and related symptoms in individuals with idiopathic hypersomnia and, in particular, whether medications may: 1. reduce subjective measures of sleepiness; 2. reduce objective measures of sleepiness; 3. reduce symptoms of cognitive dysfunction; 4. improve quality of life; and 5. be associated with adverse events. SEARCH METHODS: We searched the following databases on 4 February 2021: Cochrane Register of Studies (CRS Web), MEDLINE (Ovid, 1946 to 1 February 2021), and reference lists of articles. CRS Web includes randomized or quasi-randomized controlled trials from PubMed, Embase, ClinicalTrials.gov, the World Health Organization International Clinical Trials Registry Platform (WHO ICTRP), the Cochrane Central Register of Controlled Trials (CENTRAL), and the specialized registers of Cochrane Review Groups, including the Cochrane Epilepsy Group. We previously searched the WHO ICTRP separately when loading of ICTRP records into CRS Web was temporarily suspended. SELECTION CRITERIA: Randomized studies comparing any medication to placebo, another medication, or a behavioral intervention. DATA COLLECTION AND ANALYSIS: Two review authors independently extracted data and assessed trial quality. We contacted study authors for additional data. We collected data on adverse events from the included trials. MAIN RESULTS: We included three trials, with a total of 112 participants. Risk of bias was low for the included studies. Two pharmaceutical company-sponsored trials compared modafinil with placebo, involving 102 participants, nearly all of whom had idiopathic hypersomnia without long sleep time. Modafinil significantly improved self-reported sleepiness on the Epworth Sleepiness Scale by 5.08 points more than placebo (95% confidence interval (CI) 3.01 to 7.16; 2 studies, 101 participants; high-certainty evidence). Modafinil also significantly improved disease severity on the Clinical Global Impression of Severity scale by 1.02 points (95% CI 0.11 to 1.93; 1 study, 30 participants; moderate-certainty evidence) and resulted in a greater proportion of participants who were "much improved" or "very much improved" on the Clinical Global Impression of Change (odds ratio (OR) for improvement 5.14, 95% CI 1.76 to 15.00; 1 study, 70 participants; moderate-certainty evidence). Ability to remain awake on the Maintenance of Wakefulness Test was significantly improved with modafinil, by 4.74 minutes more than with placebo (95% CI 2.46 to 7.01; 2 studies, 99 participants; high-certainty evidence). Ratings of exhaustion and effectiveness/performance were improved with modafinil compared to placebo in one study. Number of naps per week was no different between modafinil and placebo across two studies. Participants receiving modafinil experienced more side effects, although the difference did not reach statistical significance (OR 1.68, 95% CI 0.28 to 9.94; 2 studies, 102 participants; low-certainty evidence). One trial studying 20 participants with different disorders of sleepiness included 10 participants with idiopathic hypersomnia, with or without long sleep time, and compared clarithromycin to placebo. We only included the subset of trial data for those participants with idiopathic hypersomnia, per our protocol. There were no significant differences between clarithromycin and placebo for the Epworth Sleepiness Scale, psychomotor vigilance testing, sleep inertia, other subjective ratings, or side effects. AUTHORS' CONCLUSIONS: Modafinil is effective for the treatment of several aspects of idiopathic hypersomnia symptomatology, based on studies predominantly including participants with idiopathic hypersomnia without long sleep times, with low risk of bias, and evidence certainty ranging from high to low. There is insufficient evidence to conclude whether clarithromycin is effective for the treatment of idiopathic hypersomnia. There is a clear need for additional studies testing interventions for the treatment of idiopathic hypersomnia.

Modafinil Versus Amphetamine-Dextroamphetamine For Idiopathic Hypersomnia and Narcolepsy Type 2: A Randomized, Blinded, Non-inferiority Trial.

BACKGROUND AND OBJECTIVE: Although there are several treatments for narcolepsy type 2 and idiopathic hypersomnia, studies that assess amphetamines, symptoms beyond sleepiness, and comparative effectiveness are needed. We performed a randomized, fully blinded, noninferiority trial of modafinil versus amphetamine-dextroamphetamine in these disorders. METHODS: Forty-four adults were randomized to modafinil or amphetamine-dextroamphetamine, individually titrated to a maximum of modafinil 200 mg twice daily or amphetamine-dextroamphetamine 20 mg twice daily, for 12 weeks. Primary outcome was change in Epworth from baseline to week 12, with a noninferiority threshold of 2 points. Secondary outcomes were (1) patient global impression of change measures of disease severity, sleepiness, sleep inertia, and cognition; (2) change from baseline in Hypersomnia Severity Index; and (3) change from baseline in Sleep Inertia Questionnaire. Adverse events were compared between groups. RESULTS: Epworth improved 5.0 [± standard deviation (SD) 2.7] points with modafinil and 4.4 (± SD 4.7) with amphetamine-dextroamphetamine; noninferiority of amphetamine-dextroamphetamine was not demonstrated (P = 0.11). Noninferiority of amphetamine-dextroamphetamine was demonstrated for change scores of severity, sleepiness, sleep inertia, Hypersomnia Severity Index, and Sleep Inertia Questionnaire. Dropouts due to adverse events were 31.8% for modafinil (including two severe events) and 9.1% for amphetamine-dextroamphetamine, P = 0.13. Anxiety was more common with modafinil and appetite suppression with amphetamine-dextroamphetamine. CONCLUSION: Noninferiority of amphetamine-dextroamphetamine to modafinil was not demonstrated for the primary outcome. However, amphetamine-dextroamphetamine was noninferior on multiple secondary measures of disease severity and symptomatology. These data may inform shared decision-making regarding treatment for idiopathic hypersomnia and narcolepsy type 2. REGISTRATION: Clinicaltrials.gov Registration (NCT03772314) 12/10/18. .

Neurosarcoidosis: clinical features, diagnosis, and management.

Sarcoidosis is a multisystemic granulomatous disease, which uncommonly affects nervous system. However, when present, it may affect both central and peripheral nervous systems and potentially mimics other chronic diseases of the nervous system. Pathogenesis of neurosarcoidosis remains largely unknown, and its diagnosis and management pose serious challenges to clinicians. Early diagnosis and aggressive treatment of neurosarcoidosis are necessary to produce satisfactory clinical outcomes. This review discusses clinical manifestations, current diagnostic studies, and currently available modalities for management of neurosarcoidosis.

Clinically presenting acute/subacute ischemic stroke: differential diagnosis of the non-enhanced CT hypodensity by advanced neuroimaging.

OBJECTIVES: Patients presenting to the emergency room with an acute or subacute onset of focal neurological deficits are evaluated initially by non-contrast computed tomogram (CT) of the brain. This is primarily carried out to differentiate an ischemic from hemorrhagic stroke. However, other neurological conditions may have a similar clinical presentation as well as only hypodensities on CT scan, thus mimicking ischemic stroke. This review focuses on the advanced neuroimaging modalities that help differentiate these other conditions from a cerebral infarction. METHODS: The literature was reviewed in order to ascertain what conditions would clinically and by CT mimic an acute/subacute ischemic infarction, and what advanced neuroimaging techniques would be most useful in differentiating these conditions. RESULTS: Several infectious, inflammatory, metabolic and vascular diseases were found with clinical presentations identical to subacute/acute ischemic cerebral infarction, which also could demonstrate only hypodensities on a non-enhanced CT scan. However, advanced neuroimaging techniques could readily differentiate these conditions from ischemic infarction. CONCLUSIONS: As presented in this review, although several diseases initially present a diagnostic dilemma upon presentation because of their clinical and non-enhanced CT similarities to cerebral infarction, advanced diagnostic neuroimaging readily establishes their unique pathologies.

Kinesigenic reflex epilepsy associated with a glioma in the lateral peri-rolandic region.

A patient with kinesigenic focal motor seizures induced by tongue-jaw movement had a grade III astrocytoma clearly co-localizing with the epileptic network in the appropriate peri-rolandic, motor-sensory, lingual-jaw cortical area. The clinical seizure phenomena were time-locked with the EEG epileptic activity. [Published with video sequences].

Images: Periodic Limb Movements During Sleep Noted on Ventral Thigh Surface Electromyography in an Above-the-Knee Amputated Stump.

None: Ventral thigh surface electromyography may be used to assess for periodic limb movements during sleep (PLMS) in a limb with an above-the-knee amputation. Presence of PLMS in the proximal portion of an amputated lower extremity supports theories of spinal and supraspinal mechanisms in PLMS generation, and demonstrates that intact distal motor efferent pathways and distal sensory afferent pathways are not absolutely necessary for the generation of periodic limb movements. CITATION: Chada A, Hoque R. Periodic limb movements during sleep noted on ventral thigh surface electromyography in an above-the-knee amputated stump. J Clin Sleep Med. 2019;15(8):1183-1184.

Pseudo-subarachnoid hemorrhage in a patient with acute cerebellar infarction.

OBJECTIVE: Hyperdensity in the basal cisterns on computed tomography (CT) brain scan is a diagnostic feature in subarachnoid hemorrhage. However, false enhancement of the subarachnoid space on CT scan may be seen in diffuse neurological conditions with acute presentation. This is the first reported case of a 'focal lesion' (acute cerebellar infarct) producing a 'pseudo-subarachnoid hemorrhage' secondary to increased intracranial pressure. CLINICAL PRESENTATION: A 42-year-old man presented with acute onset of left hemiataxia and neck pain. CT brain scan showed a left cerebellar infarct. During the admission, he had sudden onset of altered sensorium, and an emergency CT scan showed diffuse cerebral edema and hyperdensity of the basal cisterns. The patient then developed sudden cardiac arrest and all resuscitative measures failed. Autopsy showed no evidence of subarachnoid hemorrhage. CONCLUSION: Pseudo-subarachnoid hemorrhage is a rare clinical entity. It should be considered as a possibility in the evaluation and management of patients presenting acutely with CT brain scan showing hyperdensity of the basal cisterns and vascular imaging revealing absence of any aneurysm or vascular malformation.

Use of perfusion- and diffusion-weighted imaging in differential diagnosis of acute and chronic ischemic stroke and multiple sclerosis.

OBJECTIVE: To investigate differences in lesions and surrounding normal appearing white matter (NAWM) by perfusion-weighted imaging (PWI) and diffusion-weighted imaging (DWI) in patients with acute and chronic ischemic stroke and multiple sclerosis (MS). METHODS: Study subjects included 45 MS patients, 22 patients with acute ischemic stroke and 20 patients with chronic ischemic stroke. All subjects underwent T2-weighted imaging (WI), flair attenuated inversion recovery (FLAIR), DWI and dynamic contrast enhanced PWI. Apparent diffusion coefficient (ADC) and mean transit time (MTT) maps were generated and values were calculated in the acute and chronic ischemic and demyelinating lesions, and in NAWM for distances of 5, 10 and 15 mm. Fifty-three acute ischemic and 33 acute demyelinating lesions, and 775 chronic ischemic and 998 chronic demyelinating lesions, were examined. Univariate, multivariate and data mining analyses were used to examine the feasibility of a prediction model between different lesion types. Correctly and incorrectly classified lesions, true positive (TP), false positive (FP) and precision rates were calculated. RESULTS: Patients with acute ischemic lesions presented more prolonged mean MTT values in lesions (p=0.002) and surrounding NAWM for distances of 5, 10 and 15 mm (all p<0.0001) than those with acute demyelinating lesions. In multinomial logistic regression analysis, 65 of 86 acute lesions were correctly classified (75.6%). The TP rates were 81.1% for acute ischemic lesions and 66.7% for acute demyelinating lesions. The FP rates were 33.3% for acute ischemic and 18.9% for acute demyelinating lesions. The precision was 79.6% for classification of acute ischemic lesions and 68.8% for prediction of acute demyelinating lesions. The logistic model tree decision algorithm revealed that prolonged MTT of surrounding NAWM for a distance of 15 mm (> or =7459.2 ms) was the best classifier of acute ischemic versus acute demyelinating lesions. Patients with chronic ischemic lesions presented higher mean ADC (p<0.0001) and prolonged MTT (p=0.013) in lesions, and in surrounding NAWM for distances of 5, 10 and 15 mm (all p<0.0001), compared to the patients with chronic demyelinating lesions. Data mining analyses did not show reliable predictability for correctly discerning between chronic ischemic and chronic demyelinating lesions. The precision was 56.7% for classification of chronic ischemic and 58.9% for prediction of chronic demyelinating lesions. DISCUSSION: We found prolonged MTT values in lesions and surrounding NAWM of patients with acute and chronic ischemic stroke when compared to MS patients. The use of PWI is a promising tool for differential diagnosis between acute ischemic and acute demyelinating lesions. The results of this study contribute to a better understanding of the extent of hemodynamic abnormalities in lesions and surrounding NAWM in patients with MS.

Application of hidden Markov random field approach for quantification of perfusion/diffusion mismatch in acute ischemic stroke.

The perfusion/diffusion 'mismatch model' in acute ischemic stroke provides the potential to more accurately understand the consequences of thrombolytic therapy on an individual patient basis. Few methods exist to quantify mismatch extent (ischemic penumbra) and none have shown a robust ability to predict infarcted tissue outcome. Hidden Markov random field (HMRF) approaches have been used successfully in many other applications. The aim of the study was to develop a method for rapid and reliable identification and quantification of perfusion/diffusion mismatch using an HMRF approach. An HMRF model was used in combination with automated contralateral identification to segment normal tissue from non-infarcted tissue with perfusion abnormality. The infarct was used as a seed point to initialize segmentation, along with the contralateral mirror tissue. The two seeds were then allowed to compete for ownership of all unclassified tissue. In addition, a novel method was presented for quantifying tissue salvageability by weighting the volume with the degree of hypoperfusion, allowing the penumbra voxels to contribute unequal potential damage estimates. Simulated and in vivo datasets were processed and compared with results from a conventional thresholding approach. Both simulated and in vivo experiments demonstrated a dramatic improvement in accuracy with the proposed technique. For the simulated dataset, the mean absolute error decreased from 171.9% with conventional thresholding to 2.9% for the delay-weighted HMRF approach. For the in vivo dataset, the mean absolute error decreased from 564.6% for thresholding to 34.2% for the delay-weighted HMRF approach. The described method represents a significant improvement over thresholding techniques.

Cryptococcal meningitis presenting as pseudosubarachnoid hemorrhage.

A 50-year-old man presented with progressive visual loss, headache, and two days of confusion. A computed tomography of his head suggested subarachnoid hemorrhage with accompanying right parietal ischemic infarction. The magnetic resonance image was consistent with right parietal perisulcal pial and superficial cortical inflammation; a subjacent vasogenic edema with a 1 cm diameter abscess was also present. Funduscopy revealed bilateral multifocal choroidal lesions and retinal perivascular sheathing. He was diagnosed with pseudosubarachnoid hemorrhage secondary to cryptococcal meningitis and choroidal microabscesses with retinal inflammation after a cerebrospinal fluid (CSF) examination revealed cryptococcal yeast forms, as well as high titers of CSF cryptococcal antigen, but no CSF red blood cells.

Legal Aspects of Sleep Medicine in the 21st Century.

Multiple manifestations of sleep disorders may interact with the law, making it important to increase awareness of such interactions among clinicians. Patients with excessive sleepiness may have civil (and in some states criminal) liability if they fall asleep while driving and cause a motor vehicle accident. Employers may be held vicariously liable because of the actions of sleepy employees. Hence, awareness of causes of excessive sleepiness, such as sleep deprivation and OSA, is increasing among trucking, railroad, and other safety-sensitive occupations. Interestingly, litigation related to perioperative complications because of OSA is more frequent than nonoperative issues such as a failure to diagnose OSA. Parasomnia-associated sleep-related violence represents a challenge to clinicians because they may be asked to consider parasomnia as a possible contributing, mitigating, or exculpatory factor in criminal proceedings. Clinicians should also familiarize themselves with the legal and regulatory aspects of running an independent sleep laboratory. Sleep telemedicine practice using 21st century technology has opened novel and unique challenges to existing laws. In this review, we cover the most common interactions between sleep disorders and the law, including the challenges of excessive sleepiness and driving, other legal issues involving patients with OSA, and the liabilities associated with parasomnia disorder. We will also cover some practical legal aspects involving independent sleep laboratories and the field of sleep telemedicine.

Legal and Regulatory Aspects of Sleep Disorders.

Sleep disorders may interact with the law, making awareness important. Insufficient sleep and obstructive sleep apnea (OSA) are prevalent and associated with excessive sleepiness. Patients with excessive sleepiness may have civil or criminal liability if they fall asleep and cause a motor vehicle accident. Awareness of screening and treatment of OSA is increasing in certain industries. Parasomnia associated sleep-related violence represents a challenge to clinicians, who may be called on to consider parasomnia as a contributing, mitigating, or exculpatory factor in criminal proceedings. Improving access to sleep medicine care is an important aspect in reducing the consequences of sleep disorders.

Sleep-Disordered Breathing in Duchenne Muscular Dystrophy: An Assessment of the Literature.

STUDY OBJECTIVES: The aim of this review is to review the literature on sleep-disordered breathing in Duchenne muscular dystrophy (DMD). METHODS: PubMed was searched with an array of search terms, including "OSA," "obstructive sleep apnea," "sleep-disordered breathing," "muscular dystrophy," "neuromuscular," "Duchenne muscular dystrophy," "polysomnography," and "portable monitoring." All relevant articles were discussed. RESULTS: Eighteen research articles and 1 consensus statement were reviewed, and assessed with relevant data presented. Three early studies prior to 1990 assessed DMD associated obstructive sleep apnea. Five studies assessed positive airway pressure (PAP) ventilation and/or sleep in varying neuromuscular disorders, including a cohort with DMD. Six studies since 2000 include PSG data in exclusively DMD cohorts. Three studies involved portable monitoring (PM). CONCLUSIONS: PSG with transcutaneous CO2 capnography is an important part of the clinical care for those with DMD. The utility of PM in DMD is unclear with only 1 study to date comparing PSG to PM data. Initiation of PAP therapy using bilevel modality may prevent the need for device switching as the disease progresses.

Nocturnal Hypermotor Activity during Apnea-Related Arousals.

ABSTRACT: We present a case of a 50-year-old patient who exhibits nocturnal hypermotor activity occurring exclusively during apnea-related arousals consisting of repetitive lower extremity hip-flapping. This movement is unusual and reflects a new form of lower extremity movement associated with apnea-related arousals.

Severe Postictal Hypoxemia-Associated Seizure in a 12-Year-Old Child.

ABSTRACT: A 9 year-old girl with developmental delay and seizure disorder presented for evaluation of witnessed breathing pauses during sleep that were not associated with snoring or gasping. Polysomnography showed a generalized seizure with post ictal central apnea associated with severe desaturation and a post central apnea brief seizure. This case report discusses the pathophysiology of post-ictal desaturations and breathing abnormalities during seizures and their possible association with sudden unexpected death in epilepsy. The case also demonstrates the utility of polysomnography for the diagnosis of breathing abnormalities associated with seizures.

Continuous Positive Airway Pressure Device Time to Procurement in a Disadvantaged Population.

Introduction. The management of obstructive sleep apnea (OSA) in patients who cannot afford a continuous positive airway pressure (CPAP) device is challenging. In this study we compare time to CPAP procurement in three groups of patients diagnosed with OSA: uninsured subsidized by a humanitarian grant (Group 1), uninsured unsubsidized (Group 2), and those with Medicare or Medicaid (Group 3). We evaluate follow-up and adherence in Group 1. We hypothesize that additional factors, rather than just the ability to obtain CPAP, may uniquely affect follow-up and adherence in uninsured patients. Methods. 30 patients were in Groups 1 and 2, respectively. 12 patients were in Group 3. Time of CPAP procurement from OSA diagnosis to CPAP initiation was assessed in all groups. CPAP adherence data was collected for Group 1 patients at 1, 3, 6, and 9 months. Results. There were no significant differences between groups in gender, age, body mass index, or apnea hypopnea index. The mean time to procurement in Group 1 was shorter compared to Group 2 but not significant. Compared to both Group 1 and Group 2, Group 3 patients had significantly shorter times to device procurement. Conclusion. Time to procurement of CPAP was significantly shorter in those with Medicaid/Medicare insurance compared to the uninsured.

Paraneoplastic overlap syndrome in non-small squamous cell lung carcinoma.

This is a case of paraneoplastic overlap of limbic encephalitis and opsoclonus myoclonus in a patient with non-small squamous cell lung carcinoma.