IgG4-related pachymeningitis-Long term follow up and outcome of six patients.

OBJECTIVE: Our understanding of IgG4-RD and pachymeningitis has grown substantially, but the optimal approach for diagnosis, management, and long-term outcomes is still an area of uncertainty. METHODS: HUVAC is a database for IgG4-RD patients, this database was retrospectively evaluated for pachymeningeal disease. Demographic, clinical, serological, imaging, histopathological data, and treatment details were re-interpreted in patients with pachymeningitis. RESULTS: Among 97 patients with IgG4-RD, 6 (6.2%) had pachymeningitis. None of these patients had extracranial features, and also, in most of the patients, serum IgG4 levels were normal. Tentorium cerebelli and transverse sinus dura were the most commonly involved in the posterior fossa. During 18 months of median follow-up on steroid+-rituximab, none of them relapsed as pachymeningitis. CONCLUSION: Our patients were mainly older males with sole neurological involvement. Non-specific headache was the most common manifestation, and serum IgG4 levels were not useful for diagnosis. Typical radiology and tentorial thickening should suggest IgG4-RD and prompt an early biopsy. Moreover, accompanying hypophysitis could also be a clue. With steroids+ rituximab treatment, no relapse related to meningeal involvement was seen in long-term follow-up.

Nusinersen for adults with spinal muscular atrophy.

INTRODUCTION: Nusinersen was effective in improving motor function and survival in infantile and childhood-onset spinal muscular atrophy (SMA), and the value of real-world experiences in adult SMA patients increase gradually. Here, we present our clinical experience in adult SMA patients treated with nusinersen according to CHERISH study. MATERIAL AND METHODS: Thirty-two SMA patients treated with nusinersen were included in the study. RESULTS: Median age at nusinersen initiation was 33.5 (20.0-60.0) years and 23 of SMA patients were male. Six (18.8%) patients had SMA type 2, and 26 (81.2%) had SMA type 3. Median follow-up period of patients under nusinersen treatment was 17 months (9-21). Twenty-three patients improved by at least 3 Hammersmith Functional Motor Scale Expanded (HFMSE) points after loading doses. There was significant HFMSE score increase in type 3 patients at each time point, whereas type 2 patients seem to benefit from nusinersen loading doses, subsequently stayed stable. Motor improvement was positively correlated with baseline HFMSE scores in patients whose baseline HFMSE scores were ≤47. There was a correlation between the changes in Amyotrophic Lateral Sclerosis Functional Rating Scale Revised (ALSFRS-R) score and HFMSE scores. Ambulatory patients who could not show clinically meaningful increase in HFMSE scores improved at least 30 m by 6-min walk test (6MWT). CONCLUSION: Overall, 78% of patients have responded to treatment according to HFMSE or 6MWT. ALSFRS-R and 6MWT may be alternative tools to monitor nusinersen effect.

Interactions between the painful disorders and the autonomic nervous system.

he autonomic nervous system (ANS) controls the heart rate, blood pressure, digestion, respiration, pupillary reactivity, sweating, urination, sexual arousal, and regulates the functions of internal organs. This system provides the homeostasis of the cells, tissues, and organs throughout the body and protects against the disturbances imposed by the external and internal stressors. The ANS has three main divisions: The sympathetic nervous system (SNS), the parasympathetic nervous system (PNS), and the enteric nervous system. In general, the SNS and PNS have opposing effects. Each region belonging to the 'pain matrix' interacts with ANS. The descending system regulates pain and creates a regulatory effect by the contribution of aminergic neurotransmitters. Hypothalamus, amygdala, and periaqueductal gray are the main structures of this regulatory system. Dysfunction of the ANS is frequently observed in pain patients. The SNS induce, facilitate, or potentiate chronic pain. Increased responsiveness of injured sensory nerves to catecholamines, increased expression of α-1 adrenoreceptors on the primary afferent nociceptors and hyperalgesic skin, central sensitization rendering Aß mechanoreceptors, enhanced discharge and sympathetic sprouting in dorsal root ganglia, central sensitization, and dysfunction of the pain modulation is proposed mechanisms. In this review, the anatomical, physiological and pathological aspects of ANS and pain, and laboratory tests to evaluate autonomic functions will be discussed. Pathophysiological role of ANS in migraine, trigeminal autonomic cephalgias, trigeminal neuralgia, peripheral nerve injuries, small fiber neuropathies, myofascial pain syndrome, fibromyalgia, painful joint diseases, visceral pain, phantom limb pain, complex regional pain syndrome, and spinal cord injury will be discussed.

Isolated spinal cord granulomatous angiitis: a case report and review of the literature.

INTRODUCTION: Isolated spinal cord angiitis (ISCA) is very rare disease. But, it is frequently encountered in the differential diagnosis of atypical spinal cord syndromes. CASE PRESENTATION AND REVIEW OF THE LITERATURE: We present a 31-year-old male who presented with progressive paraparesis, and diagnosed with pathologically confirmed ISCA. Longitudinal cystic transverse myelitis was documented in spinal MRI. He responded well to cyclophosphamide and steroid combination, and no relapse was noted during the 4-year follow-up. A standard systematic analysis of the germane literature disclosed 15 more ISCA cases. In total 16 cases (mean age: 46.5, 10 males), ISCA was diagnosed with pathological evaluation in all (Biopsy in 11, Autopsy in 5). MRI lesion is characterized by usually multisegmental longitudinal and sometimes cystic expansile lesions. In seven cases, it was described as "(pseudo)tumoral" by the authors. Albeit absence of elevation of CSF protein/WBC or "compatible" spinal MRI lesion may aid to exclude ISCA to some extent, pathological confirmation is currently necessary for the diagnosis. In 11 cases, ISCA was treated similar to primary supratentorial vasculitis. Mortality rate is 31%. DISCUSSION: ISCA diagnosis, a typical example of which we have presented here, can only be established by tissue examination. However, noninvasive diagnostic criteria are critically needed. Our data suggest that this can only be possible with multinational multicenter prospective registry.

The functional and structural evaluation of small fibers in asymptomatic carriers of TTR p.Val50Met (Val30Met) mutation.

Therapeutic advances in hereditary amyloid transthyretin (ATTRv) amyloidosis with polyneuropathy extended life expectancy and delayed symptom progression especially in patients with early disease. Thus, detection and monitoring of asymptomatic carriers gained importance. However, there is still limited consensus on genetic screening of ATTRv-polyneuropathy patients' family members and diagnostic tests that must be done in the follow-up. In this study, we followed prospectively five asymptomatic carriers of a family with ATTRV30M (p.Val50Met) mutation by different diagnostic tests for three years. The carriers were followed by neurological examination, nerve conduction studies, sympathetic skin response test, heart rate variability, SFN-SIQ and DN4 questionnaires, quantitative sensory testing (QST), skin biopsy and in vivo corneal confocal microscopy. Nerve conduction studies, sympathetic skin response test and heart rate variability were normal in all for three years. Baseline QST and SFN-SIQ were normal but became abnormal during follow-up of two individuals who developed small fiber neuropathy symptoms. Baseline intraepidermal nerve fiber density was low in three carriers and decreased to below normative values in all during follow-up, while corneal sub-basal nerve density was low in all carriers compared to controls during the entire follow-up. Thus, our study showed that SFN-SIQ and QST are useful diagnostic tools to detect the transition to symptomatic ATTRv-polyneuropathy.

Post-COVID-19 longitudinally extensive transverse myelitis: is it a new entity?

INTRODUCTION: To the best of our knowledge, here we present two post-COVID19 longitudinally extensive transverse myelitis (LETM) with atypical presentations CASE PRESENTATIONS: A 44-year-old male who did not have any previous medical condition and a 73-year-old male foreigner who did not have any disease other than type 2 diabetes mellitus were admitted to our neurology clinic in the same period with similar clinical presentations of transverse myelitis. Upon admission, paraplegia and urinary-fecal incontinence were observed in their neurological examination. Neurological complaints had started within approximately 3-4 weeks following the resolution of the COVID-19 infection. Thoracic lower segment LETM was observed on spinal magnetic resonance imaging (MRI) in one of the patients, and long segment myelitis extending from the lower thoracic segment to the conus medullaris was observed in the other one. No significant diagnostic positivity was present in their diagnostic evaluation. In both cases, we assume a post-infectious etiology in terms of secondary immunogenic overreaction following COVID-19. CONCLUSION: Our patients improved with multiple treatments such as methylprednisolone, intravenous immunoglobulin, and plasmapheresis. Whether post-infectious myelitis behaves differently from other viral infections after COVID-19 is currently unclear. Long lag times appear to be a post-infectious neurological complication resulting from the host response to the virus.

Efficacy and Safety of Ketamine in Refractory/Super-refractory Nonconvulsive Status Epilepticus: Single-Center Experience.

Refractory/super-refractory nonconvulsive status epilepticus (r/srNCSE) is an acute life-threatening neurocritical entity with significant morbidity. Failure to control SE in its earlier stages leads to multiple molecular alterations in the brain such as downregulation of GABA-A and upregulation of NMDA receptors. Recently ketamine, an NMDA receptor antagonist, has gained increased attention as a therapeutic choice in controlling refractory/super-refractory SE. We aimed to analyze the efficacy and safety profile of ketamine in our center. We retrospectively identified all the patients with nonconvulsive SE who received ketamine during their follow-up in our neurological intensive care unit between 2009 and 2019. Information about demographic, clinical, and laboratory findings; concurrent antiseizure and anesthetic medications; time of initiation, dose and duration of ketamine infusion; any adverse effects and finally prognosis were collected. The effect of day of ketamine initiation and duration of infusion on ketamine efficacy were analyzed statistically. Seven patients (4 males, 3 females; age: 44-86 years) were included in the study. Encephalitis was the most common etiology. Concurrent antiseizure medications varied between 2 and 5. Six patients received midazolam before/during ketamine infusion. Ketamine was initiated 2 to 7 days after the onset of EEG monitoring and lasted 3 to 24 days with a maximum infusion dose ranging between 1 to 5 mg/kg/h. It was definitely effective in 4 patients, and possibly effective in an additional patient. Earlier initiation was correlated with higher efficacy (P = .047). There was a trend toward higher efficacy with longer duration of infusion (P = .285). Overall prognosis was poor with 29% mortality rate. Temporary hepatic failure occurred in 1 patient. Ketamine appears to be a promising drug in r/srNCSE. Earlier and prolonged infusion, as well as combination with benzodiazepines may increase its efficacy. Adverse events are rarely observed.

A case of drug-induced bullous pemphigoid associated with teriflunomide: A patient with relapsing multiple sclerosis.

BACKGROUND: There aren't many reported skin changes associated with teriflunomide use in patients with multiple sclerosis (MS) mm Only one life-threatening gross skin change has been reported so far; a patient with toxic epidermal necrolysis. There are also a few case reports about cutaneous adverse effects of teriflunomide, such as eczema, rash and palmar pustular psoriasis. METHODS: We herein report the first case of bullous drug reaction in a patient receiving teriflunomide treatment. RESULTS: A 55-year-old women with relapsing multiple sclerosis (RMS) was diagnosed teriflunomide induced bullous pemphigoid as it was detected in the first three months following the initiation of therapy. It is fully recovered after withdrawal of teriflunomide, in combination with systemic steroid treatment. DISCUSSION: We report the first case of bullous drug reaction associated with teriflunomide. Multiple drugs have been implicated in the pathogenesis of the disease so far. It is important to point out some immunosuppressants may trigger autoimmune diseases like bullous pemphigoid. CONCLUSION: Considering recently reported skin reactions associated with teriflunomide, neurologists and patients should be careful on potential warning symptoms and signs of cutaneous drug reactions of this drug.