Derrick Robertson

Medical marijuana in neurology

Constituents of the Cannabis plant, cannabinoids, may be of therapeutic value in neurologic diseases. The most abundant cannabinoids are Δ9-tetrahydrocannabinol, which possesses psychoactive properties, and cannabidiol, which has no intrinsic psychoactive effects, but exhibits neuroprotective properties in preclinical studies. A small number of high-quality clinical trials support the safety and efficacy of cannabinoids for treatment of spasticity of multiple sclerosis, pain refractory to opioids, glaucoma, nausea and vomiting. Lower level clinical evidence indicates that cannabinoids may be useful for dystonia, tics, tremors, epilepsy, migraine and weight loss. Data are also limited in regards to adverse events and safety. Common nonspecific adverse events are similar to those of other CNS ‘depressants’ and include weakness, mood changes and dizziness. Cannabinoids can have cardiovascular adverse events and, when smoked chronically, may affect pulmonary function. Fatalities are rare even with recreational use. There is a concern about psychological dependence, but physical dependence is less well documented. Cannabis preparations may presently offer an option for compassionate use in severe neurologic diseases, but at this point, only when standard-of-care therapy is ineffective. As more high-quality clinical data are gathered, the therapeutic application of cannabinoids will likely expand.

Seronegative Neuromyelitis Optica Spectrum Disorder following Exposure to Hepatitis B Vaccination

Controversy exists regarding a potential link between exposure to recombinant hepatitis B vaccine (HBV) and central nervous system demyelinating diseases. Here, we present a case of seronegative neuromyelitis optica spectrum disorder (NMOSD) following exposure to HBV. A 28-year-old man developed painful eye movements 11 days after exposure to HBV. Within 24 h, he experienced vision loss, ascending numbness, and ataxia. T-spine MRI showed a cord lesion spanning T6-T9. Brain MRI showed bilateral optic nerve contrast enhancement and a right-sided internal capsule lesion. Cerebrospinal fluid analysis was normal, including negative oligoclonal bands and normal IgG index. AQP4-IgG serology was negative. The patients visual symptoms improved after treatment with steroids and plasma exchange. He received plasma exchange weekly for 4 weeks with decreased numbness and tingling as well as improved coordination. Treatment with mycophenolate mofetil was started, and the patient remains clinically stable with near resolution of his prior symptoms. Neuromyelitis optica is characterized by optic neuritis and/or longitudinally extensive transverse myelitis. While our patient tested seronegative for AQP4-IgG (which remains negative in 10-50% of NMOSD cases, despite testing with the most sensitive assays available), he did meet NMOSD diagnostic criteria. In a literature review, we found 7 cases of NMOSD onset or relapse associated with exposure to various vaccines, but to our knowledge this represents the first published report of NMOSD onset following exposure to HBV. While causality between vaccination and CNS demyelinating disease remains elusive, it is important to report these cases to help develop safer vaccinations and provoke further inquiry into the pathogenesis of NMOSD.

Tolerability and efficacy of colestipol hydrochloride for accelerated elimination of teriflunomide

ABSTRACT Background: Teriflunomide is an oral disease modifying therapy approved for the treatment of relapsing forms of multiple sclerosis. Teriflunomide’ s pharmacokinetics (PK) contribute to its slow elimination, on average taking 6–8 months, though it can take up to 2 years in some instances. This slow elimination can become problematic in certain clinical situations – such as during pregnancy, when teriflunomide has potential teratogenic effects. In such scenarios, an accelerated elimination procedure (AEP) is recommended. Currently, AEPs with oral cholestyramine or activated charcoal are available but are restricted by adverse effects, limited administration routes, and dosing frequencies. Methods: A single-center, PK interaction study was performed in a total of 14 healthy volunteers, to investigate colestipol hydrochloride (HCl) as an alternative to cholestyramine for the elimination of teriflunomide. Participants received teriflunomide for 14 days, followed by an AEP with colestipol HCl for 15 days. Results and conclusions: The administration of colestipol HCl for 15 days was sufficient to reduce plasma teriflunomide concentrations by greater than 96%. Although colestipol HCl did not completely eliminate teriflunomide with the same effectiveness as cholestyramine, it may offer an alternative method for accelerated elimination of teriflunomide with potentially improved tolerability and more favorable dosing and administration options.

Patient perceived changes in sexual dysfunction after initiation of natalizumab for multiple sclerosis

Purpose Sexual dysfunction is a common but often overlooked secondary symptom of multiple sclerosis (MS) and can be associated with a decreased health-related quality of life (HRQoL). Natalizumab is a disease-modifying therapy approved for the treatment of relapsing forms of MS. In addition to its efficacy, those using natalizumab have shown improvement in HRQoL parameters, including fatigue and cognition. The idea that improvement in fatigue may also correlate with improvement in sexual dysfunction is the impetus for this study. Methods A single-center, open-label, single-arm, 24-week study was performed to evaluate perceived change in sexual dysfunction in MS patients treated with natalizumab. Adults with relapsing MS initiating natalizumab treatment and had a baseline level of sexual dysfunction were enrolled. The primary endpoint was change in the MS Intimacy and Sexuality Questionnaire-19 (MSISQ-19) score from baseline to week 24. Mean age of patients was 41 years, median disease duration was 7 years, and 73% of patients used at least one prior MS disease-modifying therapy. Results Natalizumab-treated patients experienced improvement in sexual dysfunction within the first 24 weeks of starting therapy, as demonstrated by the primary subscale of the MSISQ-19 questionnaire (–0.6976, p = 0.02). Conclusions Given the high prevalence of sexual dysfunction in MS patients and the significant impact it has on HRQoL, more research on this often overlooked symptom of MS could be very informative for patients that are deciding to initiate a new disease modifying therapy.

To diagnose or not to diagnose? Timing is the question: balancing early diagnosis of multiple sclerosis with misdiagnosis

Multiple sclerosis (MS) is a neurodegenerative central nervous system (CNS) demyelinating disease with clinical and radiologic heterogeneity in which a pathognomonic biomarker has yet to be uncovered. Consequently, atypical presentations of MS can present a diagnostic challenge, especially in those patients who do not initially fit the classic picture of clinically isolated syndrome (CIS) and/or those who do not fulfill the 2010 McDonald criteria for MS [1,2]. Misdiagnosis can have both negative clinical and financial impacts on the patient and healthcare system [3]. Yet, there is increased pressure to make an earlier accurate diagnosis of MS due to the possibility for early initiation of disease-modifying therapies (DMT) to have improved clinical outcomes, including long-term disability reduction [4]. Finding the balance between making an early accurate diagnosis where timely intervention can commence, while avoiding the potential for misdiagnosis, remains an important topic for continual review.

Rhabdomyolysis and autoimmune variant stiff-person syndrome

Stiff-person syndrome (SPS) is a rare neurologic disorder characterized by waxing and waning muscular rigidity, stiffness and spasms. Three subtypes have been described: paraneoplastic, autoimmune and idiopathic. Rhabdomyolysis has been described in the paraneoplastic variant, but to our knowledge no case has been reported involving the autoimmune variant. We report a case report of a 50-year-old man with history of SPS who presented with recurrent episodes of severe limb and back spasms. He was hospitalized on two separate occasions for uncontrollable spasms associated with renal failure and creatinine phosphokinase elevations of 55,000 and 22,000 U/L respectively. Laboratory tests were otherwise unremarkable. The acute renal failure resolved during both admissions with supportive management. Rhabdomyolysis has the potential to be fatal and early diagnosis is essential. It should be considered in patients who have SPS and are experiencing an exacerbation of their neurologic condition.

Unusual Late Onset of Parenchymal Neuro-Behçet Disease

Neuro-Behçet disease (NBD) is a multisystem inflammatory disorder characterized by oral lesions, genital lesions, uveitis, and neurological deficits. If left untreated, it may lead to worsening neurological function and can be fatal. Here we present a case of a 52-year-old woman who was diagnosed with Behçet disease (BD) as a teenager and had a relatively mild disease course. Decades later after her initial DB diagnosis, she presented to our hospital with a chief complaint of headache. She did not have focal neurological deficits or any active mucosal lesions. Upon further investigation, the patient was found to have multiple inflammatory changes on neuroimaging and abnormal cerebrospinal fluid (CSF), consistent with the diagnosis of NBD. She was treated with intravenous corticosteroid therapy and her symptoms resolved. Although our patient presented with minimal symptoms decades after her initial diagnosis, any neurological complaint warranted a thorough investigation for a proper diagnosis and treatment given the multisystem involvement of BD.