Substance Use and the Nervous System.

OBJECTIVE: This article informs and updates the practicing neurologist on the current landscape of known neurologic injuries linked to the use of illicit drugs, focusing on emerging agents. LATEST DEVELOPMENTS: Synthetic opioids such as fentanyl and similar derivatives have exploded in prevalence, becoming the leading cause of overdose fatalities. The higher potency of synthetic opioids compared with semisynthetic and nonsynthetic opiates poses an increased risk for unintentional overdose when found as an adulterant in other illicit drug supplies such as heroin. Conversely, misinformation about the risk of symptomatic exposure to fentanyl through casual contact with the skin and ambient air has led to misdirected fear and stigma that threatens to impede valid harm-reduction measures for fentanyl users at risk of actual overdose. Finally, during the COVID-19 pandemic, overdose rates and deaths continued to climb, especially among those who use opioids and methamphetamine. ESSENTIAL POINTS: A variety of potential neurologic effects and injuries can occur with illicit drug use owing to the diverse properties and mechanisms of action of the various classes. Many high-risk agents are not detected on standard drug screens, including so-called designer drugs, and the practicing neurologist is best served by recognizing the clinical features of the traditional toxidrome and other potential idiosyncratic effects of various illicit agents.

Acute Ischemic Stroke Presentation Masked by Falsely Localizing Motor Seizure: A Clinical Case Series.

In this case series, we describe a novel observation in which 4 patients with acute ischemic stroke secondary to large vessel occlusion and no history of seizure present with focal seizure activity localizable to a chronic, contralateral infarct. The explanation for this phenomenon is unknown but may be due to a combination of effects involving disrupted interhemispheric inhibitory connections and epileptogenic changes involving chronically infarcted tissue.

Novel likely pathogenic SLC20A variant in primary familial brain calcification.

A woman in her 30s was referred to our neurology outpatient clinic following an incidental finding of significant bilateral and symmetric basal ganglia, thalamic, cerebellar and subcortical white matter calcification on brain CT and MRI. A diagnosis of asymptomatic primary familial brain calcification (PFBC) was made. Targeted genetic testing revealed a likely pathogenic variant in the SLC20A2 gene, the most common gene in which pathogenic variants have been implicated in PFBC. These findings prompted genetic testing and brain CT of our patient's asymptomatic 64-year-old father. These tests revealed the same variant in SLC20A2 and similar brain calcification on CT in the patient's father.

MuSK Myasthenia Gravis Presenting with Bilateral Vocal Cord Abduction Paresis: A Case Report and Literature Review.

INTRODUCTION: Approximately 39% to 49% of patients with previously diagnosed acetylcholine receptor antibody-negative myasthenia gravis have been found to be muscle-specific tyrosine kinase (MuSK) antibody positive. These patients have a presentation that typically includes oculobulbar weakness, poorer response to cholinesterase inhibitors, and higher risk for acute clinical decompensation that necessitates plasma exchange. MuSK patients can require more aggressive maintenance immunosuppression earlier-on to maintain stability, often with rituximab. CASE REPORT: The authors report the case of a 45-year-old woman who presented with months of worsening hoarseness and exertional dyspnea. Laryngoscopy revealed limited abduction of vocal cords bilaterally as the source of the complaint. Examination revealed ophthalmoparesis and fatigable proximal muscle weakness. She was found to have elevated MuSK antibodies that, along with evidence of neuromuscular junction transmission defect on nerve conduction studies, confirmed the diagnosis of MuSK myasthenia gravis. She experienced no improvement with pyridostigmine and decompensated despite receiving oral steroids, requiring intubation. However, she dramatically improved with plasma exchange and has since been doing well on rituximab therapy. CONCLUSION: Dysphonia with hoarse quality secondary to vocal cord abduction paresis is a rare presentation of myasthenia gravis, as opposed to the typical flaccid dysarthria seen in bulbar myasthenia and should raise suspicion for MuSK antibody positivity. MuSK myasthenia gravis cases can be more refractory to treatment with cholinesterase inhibitors and are more likely to cause exacerbations and myasthenia crisis. Therefore, early and accurate diagnosis with appropriate antibody testing is imperative to avoid delays in treatment to prevent potentially life-threatening outcomes.

Autonomic Testing Profiles in Scans without Evidence of Dopaminergic Deficit (SWEDD).

BACKGROUND: Scans without evidence of dopaminergic deficit (SWEDDS) on 123I-FP-CIT SPECT (DAT) can occur in patients with clinical evidence of Parkinsonism. In this patient population, autonomic function testing may elucidate the underlying clinical disorder. OBJECTIVE: To evaluate SWEDD patients undergoing autonomic testing and determine the severity and pattern of autonomic dysfunction. METHODS: All patients with a diagnosis of SWEDD and formal autonomic function testing at Mayo Clinic, MN were retrospectively reviewed. Autonomic failure was quantified using composite autonomic severity score (CASS). The Modified Hoehn and Yahr score (HYS) determined Parkinsonism severity. RESULTS: Of 1,874 patients with DAT imaging at Mayo Clinic, 13 met diagnostic criteria of SWEDD. The median age of symptom onset was 56.0 (IQR 40.5-75.5). Autonomic dysfunction was present in 12/13 on ARS and/or TST. The median CASS was 2.50 (IQR 1.00-3.00). Distal anhidrosis was most common (7/13) while 3/13 had widespread anhidrosis on TST and/or QSART testing. Patients with a distal pattern of anhidrosis had a median score of 3.0 (IQR 2.38-4.25) on the HYS versus 2.0 (IQR 1.00-2.00) for those with a diffuse pattern (p = 0.048). Patients with more advanced Parkinsonism were more likely to respond to L-Dopa, with higher HYS in the dopa-responsive versus non-Dopa-responsive (p = 0.026). No correlation existed between severity of Parkinsonism, and CASS (p = 0.39). CONCLUSION: Autonomic function testing may detect autonomic dysfunction in most patients with SWEDD. The pattern of dysfunction is suggestive of the degree of clinical Parkinsonism, and autonomic testing may predict whether patients with SWEDD respond to L-Dopa.

Drugs of Abuse and the Nervous System.

PURPOSE OF REVIEW: This article discusses the neurologic complications of traditional, nontraditional, and emerging drugs of abuse. RECENT FINDINGS: The manufacture, distribution, and use of so-called designer drugs are increasing. These agents can induce dramatic neurologic manifestations and can evade identification on conventional drug-screening assays. Additionally, gabapentinoids, drug agents that are very familiar to neurologists, are being abused in the general population at increasing rates to achieve euphoric highs and potentiate the effects of opiates. Furthermore, even well-known illicit narcotics such as heroin are posing dangers above their baseline because of "lacing" with additives or substitutes such as fentanyl and related compounds. These clandestine agents increase the potency of what are thought to be typical dosages to lethal levels, thus leading to more unintentional overdose deaths. SUMMARY: The potential for short- and long-term nervous system injury from drug abuse is well established. However, it is important for the practicing neurologist to possess awareness of the features and observed sequelae of the toxidromes of both traditional and nontraditional drugs of abuse. This is because the use of both is widespread in our society and conventional drug screening can miss detection of some powerful agents, thus forcing us to maintain a high index of suspicion based on recognition of the clinical features.

An unusual presentation of late-onset Alexander's disease with slow orthostatic tremor and a novel GFAP variant.

Alexander disease (AxD) is a leukodystrophy, described in infantile, juvenile and adult onset forms, due to mutations in the glial fibrillary acid protein (GFAP) gene. Adult-onset AxD (AOAD) has a range of clinical and radiographic phenotypes with the oldest reported onset in the seventh decade.We report a case of AOAD, with onset in the eighth decade, presenting with slow variant orthostatic tremor, which has not been previously described. Genetic analysis revealed a GFAP variant (c.1158C>A) that has not been previously reported. Our case serves to expand the diagnostic spectrum of AOAD both clinically and genetically.

A Case of cutaneous large B-cell lymphoma during treatment of multiple sclerosis with fingolimod.

The authors report a case of a 69-year-old woman with multiple sclerosis treated with fingolimod for duration of over one year who subsequently developed cutaneous large B cell lymphoma. There are few reported cases of lymphoma associated with fingolimod treatment for multiple sclerosis, but rates are higher than expected in the general population. The authors hope to promote awareness of the potential risk of this medication so that more diligent disease surveillance can be performed by both prescribing practitioners of fingolimod and their patients who receive it.