Clinical Reasoning: A 23-Year-Old Man With Progressive Asymmetric Weakness and Numbness.

We report a case of a 23-year-old man who presented with progressive asymmetric weakness and numbness in his distal extremities over 4 months, with initial symptoms starting days after a coronavirus 2019 (COVID-19) vaccine booster. Initial neurologic examination was notable for distal weakness of both upper and lower extremities that was more pronounced on the left, complete areflexia, and decreased distal sensation to pinprick and vibration without loss of proprioception. Nerve conduction studies demonstrated a generalized, non-length-dependent, sensorimotor, demyelinating polyneuropathy, with conduction block seen in multiple compound muscle action potentials. Sensory nerve action potentials were normal in absolute terms but had asymmetric amplitudes.Based on the patient's nerve conduction studies, he was diagnosed with a specific immune-mediated neuromuscular disorder. He was started on intravenous immunoglobulin, but within days of the first infusions experienced a rare and potentially life-threatening complication. He received appropriate treatment and was started on alternative immunotherapy, after which his symptoms improved.Our case exemplifies the features of a specific subtype of a more common immune-mediated neuromuscular diagnosis with unique elements of history, examination, and nerve conduction studies that required interpretation in the clinical context. We also discuss a rare side effect of a commonly used immunotherapy and its risk factors and comment on the likelihood that this diagnosis may be related to a preceding COVID-19 vaccine booster.

Proposition: limbic encephalitis may represent limbic status epilepticus. A review of clinical and EEG characteristics.

Limbic encephalitis (LE) with waxing and waning neuropsychiatric manifestations including behavioral, personality, psychiatric, and memory changes can evolve over days to months. Many features of LE show remarkable overlap with the characteristics of mesial-temporal (limbic) status epilepticus (MTLSE or LSE). With LE, these prolonged impaired states are assumed not to be due to ongoing epileptic activity or MTLSE, because scalp EEGs usually show no epileptiform spike-wave activity; cycling behavioral and motor changes are attributed to LE; there may be little immediate improvement with antiepileptic drugs (AEDs); and of course, implanted electrodes are rarely used. Conversely, it is known that in pre-surgical patients with refractory limbic epilepsy, implanted electrodes have revealed limbic seizures that cannot be seen at the scalp. This paper assembles a chain of inferences to advance the proposition that refractory LE might represent LSE more often than is thought, and that implanted electrodes should be considered in some cases. We present two cases that suggest that LE was also LSE, one of which warranted implanted electrodes (case 1).

EEG Based Resting State Connectivity Changes in the Motor Cortex Associated with Upper Limb Motor Recovery in the Subacute Period Post-Stroke.

Stroke is a heterogeneous condition that would benefit from valid biomarkers of recovery for research and in the clinic. We evaluated the change in resting state connectivity (RSC) via electroencephalography (EEG) in motor areas, as well as motor recovery of the affected upper limb, in the subacute phase post-stroke. Fifteen participants who had sustained a subcortical stroke were included in this study. The group made significant gains in upper limb impairment as measured by the Upper Extremity Fugl-Meyer Assessment (UEFMA) from baseline to four months post-stroke (24.78 (SD 5.4)). During this time, there was a significant increase in RSC in the beta band from contralesional M1 to ipsilesional M1. We propose that this change in RSC may have contributed to the motor recovery seen in this group. Clinical Relevance- This study evaluates resting state connectivity measured via EEG as a neural biomarker of recovery post-stroke. Biomarkers can help clinicians understand the potential for recovery after stroke and thus help them to establish therapy goals and determine treatment plans.

Evaluation of Changes in Kinematic Measures of Three Dimensional Reach to Grasp Movements in the Early Subacute Period of Recovery from Stroke.

This study examines longitudinal data of subjects initially examined in the early subacute period of recovery following a stroke with a test of reach to grasp (RTG) kinematics in an attempt to identify changes in movement patterns during the period of heightened neural recovery following a stroke. Subjects (n=8) were a convenience sample of persons with stroke that participated in an intervention trial. Baseline Upper Extremity Fugl Meyer Assessment (UEFMA) scores ranged between 31 and 52 and ages were between 49 and 83. The UEFMA and RTG test were collected prior to intervention, immediately after the intervention (approximately 18 days later post baseline) and one month after the intervention. RTG data for the uninvolved UE was collected at the one-month session. Subjects reached for objects placed on a table 10 cm from their sternums, picking them up and placing them on a target 30 cm from their acromioclavicular joints. Data was collected using an optical motion capture system. Active makers were placed on each fingertip, metacarpophalangeal, and proximal interphalangeal joint. Four additional passive markers were placed on the dorsum of the hand, the elbow, the shoulder, and the sternum. Subjects demonstrated statistically significant improvements in reaching duration, reaching trajectory smoothness, time after peak velocity and peak grip aperture. All of these measures correlated significantly with improvements in UEFMA. Clinical Relevance- Kinematic measures of reaching and grasping collected early in the subacute period of recovery from stroke may offer insight into specific aspects of the recovery of upper extremity motor function that differ from the information gleaned from clinical scales.

Prism Adaptation Treatment Improves Inpatient Rehabilitation Outcome in Individuals With Spatial Neglect: A Retrospective Matched Control Study.

OBJECTIVE: To determine whether prism adaptation treatment (PAT) integrated into the standard of care improves rehabilitation outcome in patients with spatial neglect (SN). DESIGN: Retrospective matched control study based on information extracted from June 2017-September 2019. SETTING: Inpatient rehabilitation. PARTICIPANTS: Patients from 14 rehabilitation hospitals scoring >0 on the Catherine Bergego Scale (N=312). The median age was 69.5 years, including 152 (49%) female patients and 275 (88%) patients with stroke. INTERVENTIONS: Patients were matched 1:1 by age (±5 years), FIM score at admission (±2 points), and SN severity using the Catherine Bergego Scale (±2 points) and classified into 2 groups: treated (8-12 daily sessions of PAT) vs untreated (no PAT). MAIN OUTCOME MEASURES: FIM and its minimal clinically important difference (MCID) were the primary outcome variables. Secondary outcome was home discharge. RESULTS: Analysis included the 312 matched patients (156 per group). FIM scores at discharge were analyzed using repeated-measures analyses of variance. The treated group showed reliably higher scores than the untreated group in Total FIM, F=5.57, P=.020, partial η2=0.035, and Cognitive FIM, F=19.20, P<.001, partial η2=0.110, but not Motor FIM, F=0.35, P=.553, partial η2 =0.002. We used conditional logistic regression to examine the odds ratio of reaching MCID in each FIM score and of returning home after discharge. No reliable difference was found between groups in reaching MCID or home discharge. CONCLUSIONS: Patients with SN receiving PAT had better functional and cognitive outcomes, suggesting that integrating PAT into the standard of care is beneficial. However, receiving PAT may not determine home discharge.

Feasibility of integrative games and novel therapeutic game controller for telerehabilitation of individuals chronic post-stroke living in the community.

BACKGROUND: Intensive, adaptable and engaging telerehabilitation is needed to enhance recovery and maximize outcomes. Such services may be provided under early supported discharge, or later for chronic populations. A novel virtual reality game-based telerehabilitation system was designed for individuals post-stroke to enhance their bimanual upper extremity motor function, cognition, and wellbeing. OBJECTIVES: To evaluate the feasibility of novel therapeutic game controller and telerehabilitation system for home use. METHODS: Individuals chronic post-stroke and their caregivers were recruited (n = 8 + 8) for this feasibility study. One was a screen failure and seven completed 4 weeks (20 sessions) of home-based therapy with or without remote monitoring. Standardized clinical outcome measures were taken pre- and post-therapy. Game performance outcomes were sampled at every session, while participant and caregiver subjective evaluations were done weekly. RESULTS: There was a 96% rate of compliance to protocol, resulting in an average of 13,000 total arm repetitions/week/participant. Group analysis showed significant (p <.05) improvements in grasp strength (effect size [ES] = 0.15), depression (Beck Depression Inventory II, ES = 0.75), and cognition (Neuropsychological Assessment Battery for Executive Function, ES = 0.46). Among the 49 outcome variables, 36 variables (73.5%) improved significantly (p = .001, binomial sign test). Technology acceptance was very good with system rating by participants at 3.7/5 and by caregivers at 3.5/5. CONCLUSIONS: These findings indicate the feasibility and efficacy of the system in providing home-based telerehabilitation. The BrightBrainer system needs to be further evaluated in randomized control trials and with individuals early post-stroke.

Cannabidiol Treatment for Refractory Seizures in Sturge-Weber Syndrome.

BACKGROUND: Sturge-Weber syndrome results in leptomeningeal vascular malformations, medically refractory epilepsy, stroke(s), and cognitive impairments. Cannabidiol, a cannabinoid without psychoactive properties, has been demonstrated in preclinical models to possibly have anticonvulsant, antioxidant, and neuroprotective actions. METHODS: Five subjects with Sturge-Weber syndrome brain involvement and treatment-resistant epilepsy were enrolled. Motor seizure frequency, quality of life, and adverse events were recorded from the eighth week of the pretreatment period, eight weeks after starting maintenance dose (week 14), and the most recent visit. RESULTS: Four subjects had data through week 14, one of whom initially withdrew for lack of efficacy but because of other benefits re-enrolled with a lower dose. Two subjects at week 14 and three subjects with bilateral brain involvement had at the last visit a greater than 50% seizure reduction, reported an improved quality of life, and remained on cannabidiol 63-80 weeks after starting the drug. Three subjects reported mild side effects considered related to cannabidiol. CONCLUSION: This study suggests that cannabidiol may be well tolerated as adjunctive medication for seizure management and provides initial data supporting further study of cannabidiol in individuals with Sturge-Weber syndrome.

Anticonvulsant Efficacy in Sturge-Weber Syndrome.

OBJECTIVE: We analyzed individuals with epilepsy due to Sturge-Weber syndrome to determine which anticonvulsants provided optimal seizure control and which resulted in the fewest side effects. METHODS: One-hundred-eight records from a single center were retrospectively analyzed for Sturge-Weber syndrome brain involvement, epilepsy, Sturge-Weber syndrome neuroscores, and currently used anticonvulsants. RESULTS: Of the fourteen anticonvulsants that had been employed, the most often used agents were oxcarbazepine or carbamazepine, and levetiracetam. Individuals whose seizures at the most recent visit were fully controlled (seizure-free) for 6 months or longer were more likely to have ever tried, or currently used, oxcarbazepine or carbamazepine than those with uncontrolled seizures. Thirty-nine of 69 individuals (56.5%) were seizure-free with oxcarbazepine or carbamazepine history versus 11 of 35 individuals (31.4%) who had not taken these agents (P < 0.05); 38 of 62 patients (61.3%) were seizure-free while currently taking these anticonvulsants versus 12 of 42 (28.6%) not taking them (P < 0.01). Patients with seizure control for 6 months or longer were less likely to have ever tried, or to currently be taking, levetiracetam than those without control. Sixteen of 56 individuals (28.6%) were seizure-free with levetiracetam history versus 34 of 48 (70.8%) without it (P < 0.001); 14 of 43 individuals (32.6%) were seizure-free and currently taking levetiracetam versus 36 of 61 (59.0%) not taking it (P < 0.01). When topiramate was added as second-line medication, five of nine patients (55.6%) experienced decreased seizure severity, and worsening of glaucoma was not reported. CONCLUSIONS: Carbamazepine and oxcarbazepine were associated with better seizure control than levetiracetam in this Sturge-Weber syndrome cohort and so may be preferred as the initial therapy. When used as adjunctive therapy, topiramate was effective in this limited analysis without a clear increased incidence of glaucoma.

Leveraging a Sturge-Weber Gene Discovery: An Agenda for Future Research.

Sturge-Weber syndrome (SWS) is a vascular neurocutaneous disorder that results from a somatic mosaic mutation in GNAQ, which is also responsible for isolated port-wine birthmarks. Infants with SWS are born with a cutaneous capillary malformation (port-wine birthmark) of the forehead or upper eyelid which can signal an increased risk of brain and/or eye involvement prior to the onset of specific symptoms. This symptom-free interval represents a time when a targeted intervention could help to minimize the neurological and ophthalmologic manifestations of the disorder. This paper summarizes a 2015 SWS workshop in Bethesda, Maryland that was sponsored by the National Institutes of Health. Meeting attendees included a diverse group of clinical and translational researchers with a goal of establishing research priorities for the next few years. The initial portion of the meeting included a thorough review of the recent genetic discovery and what is known of the pathogenesis of SWS. Breakout sessions related to neurology, dermatology, and ophthalmology aimed to establish SWS research priorities in each field. Key priorities for future development include the need for clinical consensus guidelines, further work to develop a clinical trial network, improvement of tissue banking for research purposes, and the need for multiple animal and cell culture models of SWS.

The Association between Specific Substances of Abuse and Subcortical Intracerebral Hemorrhage Versus Ischemic Lacunar Infarction.

BACKGROUND: Hypertension damages small vessels, resulting in both lacunar infarction and subcortical intracerebral hemorrhage (ICH). Substance abuse has also been linked to small vessel pathology. This study explores whether the use of specific substances (e.g., cocaine, tobacco) is associated with subcortical ICH over ischemia in hypertensive individuals. METHODS: Patients with hypertension, admitted with lacunar infarcts (measuring <2.0 cm) or subcortical ICH, were included in analysis. Brain MRIs and head CTs were retrospectively reviewed along with medical records. Demographic information and history of substance use (illicit/controlled: cocaine, heroin, marijuana, benzodiazepines, and methadone; alcohol; and tobacco) was obtained. "Current use" and "history of use" were determined from patient history or a positive toxicology screen. "Heavy use" was defined as: smoking- ≥0.5 packs per day or 10 pack-years; alcohol- average of >1 drink per day (women), >2 drinks per day (men). Logistic regression was performed with ICH as the dependent variable comparing those presenting with ICH to those presenting with ischemia. RESULTS: Of the 580 patients included in analysis, 217 (37%) presented with ICH. The average age was similar between the two groups (64.7 versus 66.3 years). Illicit/controlled drug use was associated with a significantly increased risk of ICH over stroke in unadjusted models (25 versus 15%, p = 0.02), with the largest effect seen in users ≥65 years old (not statistically significant). Smoking was associated with ischemia over ICH in a dose-dependent manner: any history of smoking OR 1.84, CI 1.19-2.84; current use OR 2.23, CI 1.37-3.62; heavy use OR 2.48, CI 1.50-4.13. Alcohol use was not preferentially associated with either outcome (p = 0.29). CONCLUSION: In hypertensive patients, tobacco use is associated with an increased risk of subcortical ischemia compared to ICH, while use of illicit/controlled substances appears to be predictive of hemorrhage.