Neuro-Sweet Syndrome: A Diagnostic Conundrum.

Sweet Syndrome presents as acute fever, leucocytosis and characteristic skin plaques. It can involve many organ systems but rarely affects the nervous system. We report the case of a 51-year-old female that presented with fever, rash, headache and encephalopathy. Brain magnetic resonance imaging showed extensive T2 hyperintensities involving cerebral hemispheres, cerebellum, and brainstem. A skin biopsy revealed dermal infiltration by neutrophils consistent with Sweet Syndrome. She started steroid treatment with a good clinical response. Further questioning revealed that she had a similar episode 10 years prior that had been diagnosed as acute disseminated encephalomyelitis. Neuro-Sweet Syndrome can present with a great array of symptoms and relapses over long periods of time making the diagnosis difficult without a high degree of suspicion. Clinicians should consider this syndrome in the setting of acute encephalitis with white matter lesions that are highly responsive to steroids particularly in the presence of previous similar symptoms.

Progressive multifocal leukoencephalopathy without overt immunosuppression.

Progressive multifocal leukoencephalopathy (PML) is a central nervous system disease caused by the human polyomavirus 2 that usually occurs in a setting of immunodeficiency. PML without overt immunosuppression is considered a rare occurrence but has been described in multiple previous case reports and series. Its prevalence, overall frequency, and prognosis are largely unknown. This is a single-center retrospective review of all University of Florida cases with the ICD10 PML diagnosis code (A81.2). PML without overt immunosuppression was defined as absence of human immunodeficiency virus (HIV) infection, hematological malignancy, immunomodulatory/-suppressive medications, autoimmune conditions with a propensity for PML (sarcoidosis, systemic lupus erythematosus). Cases that did not fulfill criteria for clinically or histologically definite PML were excluded. Of 52 patients with the ICD10 code A 81.2, 17 fulfilled definite diagnostic criteria for PML. Overt immunosuppression was identified in 15/17 (88.2%) cases (10/17 (58.8%): human immunodeficiency virus; 5/17 (29.4%): immunomodulatory/-suppressive medication). Two/seventeen (11.8%) cases were consistent with PML without overt immunosuppression. Possible contributing factors were a preceding dog bite and mild hypogammaglobulinemia M (39 mg/dL) in case 1 and significant alcohol use without evidence for liver disease in case 2. Both cases were fatal within 6 (case 1) and 2 (case 2) months. The results suggest that PML without overt immunosuppression may be more common than previously described. Therefore, PML should be considered even in the absence of overt immunosuppression if clinical and radiographic findings are suggestive of the diagnosis.

Rituximab in Refractory Myositis and Acute Neuropathy Secondary to Checkpoint Inhibitor Therapy.

Checkpoint inhibitor immunotherapies have been one of the latest advances through the last decade in the treatment of various cancers. As their use is increasing so is the knowledge of their complications which can affect various organ systems including the central and peripheral nervous systems. Management of these complications requires stopping the offending agent and in some cases treating with immunosuppressive agents like intravenous steroids. Physicians can face challenging situations if patients are unresponsive to steroids, intravenous immunoglobulins (IVIG), and plasmapheresis (PLEX). There are no formal guidelines to help in the management of such patients.  We present an 85-year-old male with a past medical history of renal cell carcinoma status post nephrectomy who was admitted with diplopia, eyelid ptosis, dysphagia, dysphonia, dyspnea, and generalized weakness. He was started on nivolumab and ipilimumab 10 days prior to presentation. Laboratory studies showed an elevated erythrocyte sedimentation rate, C-reactive protein, and creatine phosphokinase, and an unrevealing lumbar puncture. Acetylcholine receptor (AChR) and muscle-specific kinase (MuSK) antibodies were negative. Electromyography and nerve conduction studies showed axonal and demyelinating sensorimotor neuropathy with no significant decrement on 3 Hz repetitive stimulation. Thyroid function tests were concerning for thyroiditis and anti-thyroid peroxidase antibodies were positive. Together, these findings led to the diagnosis of refractory myositis and acute neuropathy along with autoimmune thyroiditis from nivolumab and ipilimumab immunotherapy. His symptoms were unresponsive to a 5-day course of steroids, intravenous immunoglobulins, and plasmapheresis. He was then started on rituximab with significant improvement in ptosis, dysphagia, dysphonia, and proximal weakness. Immune checkpoint inhibitors (ICI) are associated with an increased risk for the development of various autoimmune conditions. Treatment involves discontinuation of the offending drug and initiation of immunosuppressive therapy. This case is interesting as it demonstrates the importance of the awareness of the neurological complications of the checkpoint inhibitor therapies and the beneficial role of rituximab in patients who are unresponsive to initial immunosuppressive therapies including steroids, IVIG, and PLEX.

Pain as a significant symptom in patients with periodic paralysis-A cross-sectional survey.

INTRODUCTION: Periodic paralysis (PP) is thought to be limited to episodes of muscle weakness, but there are reports of fibromyalgia-like pain in PP. We aimed to evaluate pain and comorbid sleep, fatigue, and mood disorders in PP patients. METHODS: We administered a cross-sectional survey to PP patients at the 2019 Periodic Paralysis Conference. The survey consisted of the Brief Pain Inventory, Widespread Pain Index, Pittsburgh Sleep Quality Index, Modified Fatigue Impact Scale, and ten-question Center for Epidemiologic Studies Depression Scale (CESD-10). Descriptive statistics for PP patients were calculated and compared with earlier studies. RESULTS: Forty-four individuals with PP took the survey. Of these patients, 52.3% reported a moderate to severe interference of pain on their lives, and 45.5% met the study criteria for fibromyalgia. Patients with SCN4A mutations had higher rates of fibromyalgia than the next most prevalent gene mutation, CACNA1S. In patients with pain, there were increased rates of comorbid fatigue, depression, and poor sleep quality. DISCUSSION: Pain, akin to fibromyalgia, is a significant symptom of PP and can affect quality of life. Pain in PP was more prevalent than in the general population, at a rate comparable with other chronic neuromuscular disease groups. PP patients could benefit from a multidisciplinary approach to assess their pain, sleep, fatigue, and mood.

Squamous cell carcinoma of the base of the tongue mimicking bulbar-onset amyotrophic lateral sclerosis.

One-third of patients with amyotrophic lateral sclerosis (ALS) present with bulbar symptoms, exhibiting progressive dysphagia and dysarthria. In comparison, squamous cell carcinoma (SCC) of the tongue can cause tongue paralysis secondary to hypoglossal nerve infiltration. In rare cases, SCC can mimic motor neuron disease. Here, we describe a patient with SCC of the base of the tongue related to human papillomavirus infection who was initially misdiagnosed with bulbar-onset ALS.

Leucoencephalopathy with brain stem and spinal cord involvement and lactate elevation: a novel mutation in the DARS2 gene.

Leucoencephalopathy with brainstem and spinal cord involvement and lactate elevation (LBSL) is a very rare autosomal recessive, slowly progressive neurological disorder characterised by distinctive clinical findings including cerebellar, pyramidal and dorsal column dysfunction. This is caused by a mutation in the DARS2 gene, which encodes mitochondrial aspartyl-tRNA synthetase. MRI shows distinctive abnormalities in the cerebral white matter and specific brain stem and spinal cord tracts. Here, we present a case of LBSL, with a novel c.1192-2A>G mutation.

Neurologic and neuroscience education: Mitigating neurophobia to mentor health care providers.

Neurologic disorders are among the most frequent causes of morbidity and mortality in the United States. Moreover, the current shortfall of neurologists is expected to worsen over the coming decade. As a consequence, many patients with neurologic disorders will be treated by physicians and primary care providers without formal neurologic training. Furthermore, a pervasive and well-described fear of neurology, termed neurophobia, has been identified in medical student cohorts, residents, and among general practitioners. In this article, members of the American Academy of Neurology A.B. Baker Section on Neurological Education review current guidelines regarding neurologic and neuroscience education, contextualize the genesis and the negative consequences of neurophobia, and provide strategies to mitigate it for purposes of mentoring future generations of health care providers.

Presence of both anti-contactin 1 and anti-neurofascin 140 antibodies in a case of chronic inflammatory demyelinating polyneuropathy.

Chronic inflammatory demyelinating polyneuropathy (CIDP) is an acquired disorder of peripheral nerves and nerve roots. Its cause is unknown, but recently antibodies to nodal and paranodal proteins have been discovered in a small subset of CIDP patients. These contactin and neurofascin-related immune-mediated neuropathies are thought to be variants of CIDP and often respond suboptimally to standard therapy. Here, we report a patient with both anti-contactin 1 and anti-neurofascin 140 antibodies whose presentation resembled phenotypes of both CIDP variants.

Wernekink commissure syndrome with palatal myoclonus at onset: a case report and review of the literature.

BACKGROUND: Wernekink commissure syndrome causes a peculiar combination of internuclear ophthalmoplegia, dysarthria, and delayed-onset palatal myoclonus. Palatal myoclonus is thought to be secondary to delayed hypertrophic degeneration of the bilateral inferior olivary nuclei secondary to involvement of bilateral dentatoolivary tract. We describe a case of a patient with early-onset palatal myoclonus. CASE PRESENTATION: A 53-year-old Caucasian man with several vascular risk factors presented to our emergency room with slurred speech, double vision, difficulty with swallowing and walking, and rhythmic contractions of the soft palate. Brain magnetic resonance imaging showed an acute infarct of the right caudal midbrain and an old infarct of the right medulla. We hypothesize that the cause of early palatal myoclonus in our patient was a two-hit mechanism with degeneration of the right olivary nucleus resulting from prior right medullary lacunar stroke with the new infarct affecting the dentato-rubro-olivary tract on the left side, causing bilateral dysfunction initiating palatal myoclonus. CONCLUSIONS: Wernekink commissure syndrome with palatal myoclonus at onset suggests the presence of a prior ischemic insult in the medulla. Careful examination is important to identification of this presentation.

Merkel Cell Carcinoma with Distant Metastasis to the Clivus Causing Symptoms Mimicking Tolosa-Hunt Syndrome: A Case Report and Literature Review.

Merkel cell carcinoma (MCC) is an uncommon but highly malignant neuroendocrine tumor of the skin. MCC can metastasize, but involvement of the central nervous system is rare. Here, we report a case of rapidly progressing metastatic MCC to the clivus and bilateral cavernous sinus in an immunocompromised patient. This case is unique in that it is the first case report showing MCC metastasis to the clivus from a distant site. It also demonstrates that a MCC metastasis can masquerade with symptoms of Tolosa-Hunt syndrome. A literature review on MCC with CNS metastasis is presented.

Acute Demyelinating Polyneuropathy as Presentation of Hereditary Neuropathy With Liability to Pressure Palsies in a Patient Who Exercised Regularly in the Army.

Acute generalized neuropathy as the presenting manifestation of hereditary neuropathy with liability to pressure palsies (HNPP) is rare. We report a 19-year-old Army recruit who exercised regularly for 9 months and presented with 2 weeks of numbness, tingling, and weakness in both upper and lower extremities, starting 2 weeks after influenza vaccination and 1 day after vigorous exercise. Based on acute onset, clinical examination and electrophysiological findings, Guillain-Barre syndrome was diagnosed, and intravenous immunoglobulin was administered with minimal improvement. The presence of high foot arches and scapular winging raised suspicion of HNPP, confirmed by genetic testing. The role of the influenza vaccine in the development of symptoms is discussed. This case highlights the fact that HNPP can present as an acute generalized neuropathy even in people who train regularly. Careful history, physical examination, and evidence of entrapment neuropathies in nerve conduction study can aid in the diagnosis.

Response to immunotherapy in a patient with adult onset Leigh syndrome and T9176C mtDNA mutation.

Leigh syndrome is a mitochondrial disease caused by mutations in different genes, including ATP6A for which no known therapy is available. We report a case of adult-onset Leigh syndrome with response to immunotherapy. A twenty year-old woman with baseline learning difficulties was admitted with progressive behavioral changes, diplopia, headaches, bladder incontinence, and incoordination. Brain MRI and PET scan showed T2 hyperintensity and increased uptake in bilateral basal ganglia, respectively. Autoimmune encephalitis was suspected and she received plasmapheresis with clinical improvement. She was readmitted 4 weeks later with dysphagia and aspiration pneumonia. Plasmapheresis was repeated with resolution of her symptoms. Given the multisystem involvement and suggestive MRI changes, genetic testing was done, revealing a homoplasmic T9176C ATPase 6 gene mtDNA mutation. Monthly IVIG provided clinical improvement with worsening when infusions were delayed. Leigh syndrome secondary to mtDNA T9176C mutations could have an autoimmune mechanism that responds to immunotherapy.

Pediatric familial neuromyelitis optica in two sisters with long term follow-up.

Neuromyelitis optica causes bilateral optic neuritis and longitudinal extensive transverse myelitis. Although usually sporadic, 3% of cases of neuromyelitis optica are familial. The interval over which attacks continue and the long term prognosis for pediatric-onset neuromyelitis optica are not well defined. We describe two patients with pediatric familial neuromyelitis optica with the longest clinical follow-up of a pediatric case reported in the literature to our knowledge. One woman developed blindness with bilateral eye involvement within a few weeks at age 3. This was followed by transverse myelitis with paraparesis at age 19 leading to diagnosis of neuromyelitis optica. Her serum anti-aquaporin 4 antibody was later found to be positive. She continued with sporadic myelitis-related relapses but remained ambulant until age 40 when she had a more severe relapse. There was evidence of longitudinal extensive T2 hyperintensity in the thoracic spinal cord. Her sister also developed blindness at age 3.5 followed by myelitis 1year later with multiple relapses of gait impairment until her death from pneumonia at age 21. These patients represent the rare occurrence of neuromyelitis optica in children within the same family and show that this disease can have prolonged periods of remission but a continued tendency to relapse, supporting the need for lifelong immunosuppression.