Mateus Mistieri Simabukuro

Clinical and Immunologic Investigations in Patients With Stiff-Person Spectrum Disorder

IMPORTANCE Symptoms of stiff-person syndrome (SPS), stiff-limb syndrome (SLS), or progressive encephalomyelitis with rigidity, myoclonus, or other symptoms (SPS-plus) can occur with several autoantibodies, but the relative frequency of each antibody, syndrome specificity, and prognostic implications are unclear. OBJECTIVE To report the clinical and immunologic findings of a large cohort of patients with stiff-person spectrum disorder (SPSD), including SPS, SLS, and SPS-plus. DESIGN, SETTING, AND PATIENTS This study retrospectively examined a case series (January 1, 1998, through December 31, 2014) of immunologic investigations performed in a neuroimmunology referral center. The study included 121 patients with clinical features of SPSD. Data analysis was performed from July 1, 2015, through November 1, 2015. MAIN OUTCOMES AND MEASURES Analysis of clinical-immunologic associations, including autoantibodies to 8 proteins expressed in inhibitory synapses. RESULTS The median age of the patients was 51 years (interquartile range, 40-61 years), and 75 (62.0%) were female. Fifty (41.3%) had SPS, 37 (30.6%) had SPS-plus, 24 (19.8%) had SLS, and 10 (8.3%) had SPS or SLS overlapping with ataxia, epilepsy, or encephalitis. Fifty-two patients (43.0%) had glutamic acid decarboxylase (GAD65) antibodies (2 with γ-aminobutyric acid-A [GABA-A] receptor antibodies), 24 (19.8%) had α1-subunit of the glycine receptor (GlyR) antibodies (2 with GAD65 antibodies), 5 (4.1%) had other antibodies, and 40 (33.1%) tested negative for antibodies. None had gephyrin or glycine transporter antibodies. Among the main immunologic groups (GAD65 antibodies, GlyR antibodies, and antibody negative), those with GAD65 antibodies were more likely to be female (45 [86.5%] of 52, 8 [36.4%] of 22, and 18 [45.0%] of 40, respectively; P < .001), have systemic autoimmunity (34 [65.4%] of 52, 7 [31.8%] of 22, and 13 [32.5%] of 40, respectively; P = .004), and have longer delays in being tested for antibodies (median, 3 vs 0.5 and 1 year; P < .001). Patients with GAD65 antibodies were more likely to develop SPS (27 [51.9%] of 52) or overlapping syndromes (8 [15.4%] of 52) than patients with GlyR antibodies (5 [22.7%] and 0 [0%] of 22, respectively), who more often developed SPS-plus (12 [54.5%] of 22 vs 7 [13.5%] in those with GAD65 antibodies); antibody-negative patients had an intermediate syndrome distribution. In multivariable analysis, symptom severity (P = .001) and immunologic group (P = .01) were independently associated with outcome. Compared with patients with GlyR antibodies, those with GAD65 antibodies (odds ratio, 11.1, 95% CI, 2.3-53.7; P = .003) had worse outcome. Patients without antibodies had similar outcome than patients with GlyR antibodies (odds ratio, 4.2, 95% CI, 0.9-20.0; P = .07). CONCLUSIONS AND RELEVANCE In SPSD, symptom severity and presence and type of antibodies are predictors of outcome.

Sleep disorder, chorea, and dementia associated with IgLON5 antibodies

A novel syndrome characterized by a distinctive sleep disorder accompanied by variable symptoms of brainstem involvement and a highly restricted haplotype was recently described in association with antibodies to a neuronal cell adhesion protein named IgLON5. Because of the symptoms and chronic disease progression, most of these patients are primarily seen by specialists in sleep and neurodegenerative disorders. Since the initial description of this encephalopathy in 2014, only 1 additional patient has been reported.1 In order to improve clinical recognition we report a new patient who presented with the characteristic sleep dysfunction and subsequently developed chorea.

Native Valve Endocarditis due to Enterococcus hirae Presenting as a Neurological Deficit

Enterococcus hirae is a rare isolate in clinical specimens. We describe a case of native aortic valve endocarditis in a 56-year-old man. This is the third reported case of endocarditis due to this organism, the first without recurrence of endocarditis and the first presenting as a neurological deficit.

Unilateral non traumatic vertebral artery dissection with cervical spinal cord infarction

A 45-year old male patient with diabetes presented neck pain with paresthesia and paresis in upper limbs. Physical examination: proximal paraparesis, hyporeflexia and hypoesthesia in the upper limbs. MRI: ischemia in the right hemi-spinal cord (Fig 1), associated to right vertebral artery (VA) dissection (Fig 2). Although more frequently VA dissection causes transient ischemic attack or stroke1, there are few reported cases of ischemia of the cervical cord. VA branches may feed the cervical part of the anterior spinal artery on one or both sides and its occlusion by VA dissection may cause hypoperfusion in this territory2.

Rapidly Progressive Dementia: Prevalence and causes in a Neurologic Unit of a Tertiary Hospital in Brazil.

Background: Rapidly progressive dementia (RPD) is usually associated with Creutzfeldt-Jakob disease, a fatal condition. Current advances in the understanding of immune-mediated diseases allow the diagnosis of previously unrecognized treatable RPDs. Objective of the Study: The objective of the study was to describe the prevalence and causes of RPD in a neurology service, identifying potentially reversible causes. Methods: We carried out a cross-sectional evaluation of all patients admitted to the neurology unit of a tertiary hospital in Brazil between March 2012 and February 2015. We included patients who had progressed to moderate or severe dementia within a few months or up to 2 years at the time of hospitalization, and used multivariable logistic regression analysis to identify factors associated with a favorable outcome. Results: We identified 61 RPD (3.7%) cases among 1648 inpatients. Mean RPD patients’ age was 48 years, and median time to progression was 6.4 months. Immune-mediated diseases represented the most commonly observed disease group in this series (45.9% of cases). Creutzfeldt-Jakob disease (11.5%) and nonprion neurodegenerative diseases (8.2%) were less common in this series. Outcome was favorable in 36/61 (59.0%) RPD cases and in 28/31 (89.3%) of immune-mediated cases. Favorable outcome was associated with shorter time from symptom onset to diagnosis and abnormal cerebrospinal fluid findings. Conclusions: Immune-mediated diseases were the most common cause of RPD in this series. Timely evaluation and diagnosis along with institution of appropriate therapy are required in RPD, especially in view of potentially reversible causes.

Teaching NeuroImages: Limbic encephalitis associated with relapsing polychondritis

A 43-year-old man presented with subacute fever, costochondritis, headache, seizures, and amnesia. Brain MRI (figure) showed bilateral temporal lobe hyperintensities. CSF revealed 105 white cells/mm3 (77% lympho-monocytes), elevated protein, and normal glucose. Infection and paraneoplastic/autoimmune workup was negative. He improved after corticosteroid treatment.

A successful case of anti-NMDAR encephalitis without tumor treated with a prolonged regimen of plasmapheresis

Anti-NMDA receptor encephalitis is a severe but treatable autoimmune disease of the CNS. However, the use of immunotherapy and long-term outcomes have yet to be defined for this disease. We describe a case of an 18-year-old male diagnosed with anti-NMDAR encephalitis not associated with tumor, which did not respond to initial treatment with immunoglobulin, followed by corticosteroids, cyclophosphamide and evolved with significant clinical improvement after a prolonged course of plasmapheresis. Although it is not possible to affirm the good outcome was due solely to the prolonged plasmapheresis regimen, recently published data shows that improvement may take weeks or months to occur. This case discloses another therapeutic possibility for patients with refractory disease who fail to respond to recommended first-line and second-line therapy.

Intracranial germinoma causing cerebral haemiatrophy and hypopituitarism

A young woman presented with primary amenorrhoea, progressive haemiparesis, visual disturbance, dementia and focal motor seizures. Investigations showed hypopituitarism, unilateral cerebral atrophy and inflamed cerebrospinal fluid. A trans-sphenoidal biopsy gave a unifying diagnosis of a pituitary germinoma.

The importance of recognizing faciobrachial dystonic seizures in rapidly progressive dementias

Background Creutzfeldt-Jakob Disease (CJD) is the prototypical cause of rapidly progressive dementia (RPD). Nonetheless, efforts to exclude reversible causes of RPD that mimic prion disease are imperative. The recent expanding characterization of neurological syndromes associated with antibodies directed against neuronal cell surface or sympathic antigens, namely autoimmune encephalitis is shifting paradigms in neurology. Such antigens are well known proteins and receptors involved in synaptic transmission. Their dysfunction results in neuropsychiatric symptoms, psychosis, seizures, movement disorders and RPD. Faciobrachial dystonic seizure (FBDS) is a novel characterized type of seizure, specific for anti-LGI1 encephalitis. Objective In order to improve clinical recognition we report the cases of two Brazilian patients who presented with characteristic FDBS (illustrated by videos) and anti-LGI1 encephalitis. Methods We have included all patients with FBDS and confirmed anti-LGI1 encephalitis and video records of FDBS in two tertiary Brazilian centers: Department of Neurology of Hospital das Clínicas, Sao Paulo University, Sao Paulo, Brazil and Hospital Geral de Fortaleza, Fortaleza, Brazil between January 1, 2011 and December 31, 2015. Results Both patients presented with clinical features of limbic encephalitis associated with FBDS, hyponatremia and normal CSF. None of them presented with tumor and both showed a good response after immunotherapy. Conclusion FBDSs may be confounded with myoclonus and occurs simultaneously with rapid cognitive decline. Unawareness of FDBS may induce to misdiagnosing a treatable cause of RPD as CJD.

Autoimmune encephalitis and anti-GAD/GABA-A receptor antibodies

Related articles PET-positive extralimbic presentation of anti-glutamic acid decarboxylase antibody-associated encephalitis Authors’ response To the Editor,We refer to the publication of Kojima et al 2014: “PET-positive extralimbic presentation of anti-glutamic acid decarboxylase antibody-associated encephalitis”. Neurological disorders associated with antibodies against cell surface and synaptic proteins are fascinating diseases that have changed paradigms in neurological practice, mainly because these disorders were previously unknown and/or mischaracterized (Leypoldt et al., 2014). In a recent report, Kojima et al. (2014) described [...]