Acute management of a stroke-like episode in MELAS syndrome: What should we know?

•Acute management of SLEs differs from usual therapy in classic stroke patients.•IV L-Arginine should be administered urgently in the setting of a SLE.•If mental status is altered, an EEG should be performed to rule out a non-convulsive status.

Clinical, morphological and genetic characterization of Brody disease: an international study of 40 patients.

Brody disease is an autosomal recessive myopathy characterized by exercise-induced muscle stiffness due to mutations in the ATP2A1 gene. Almost 50 years after the initial case presentation, only 18 patients have been reported and many questions regarding the clinical phenotype and results of ancillary investigations remain unanswered, likely leading to incomplete recognition and consequently under-diagnosis. Additionally, little is known about the natural history of the disorder, genotype-phenotype correlations, and the effects of symptomatic treatment. We studied the largest cohort of Brody disease patients to date (n = 40), consisting of 22 new patients (19 novel mutations) and all 18 previously published patients. This observational study shows that the main feature of Brody disease is an exercise-induced muscle stiffness of the limbs, and often of the eyelids. Onset begins in childhood and there was no or only mild progression of symptoms over time. Four patients had episodes resembling malignant hyperthermia. The key finding at physical examination was delayed relaxation after repetitive contractions. Additionally, no atrophy was seen, muscle strength was generally preserved, and some patients had a remarkable athletic build. Symptomatic treatment was mostly ineffective or produced unacceptable side effects. EMG showed silent contractures in approximately half of the patients and no myotonia. Creatine kinase was normal or mildly elevated, and muscle biopsy showed mild myopathic changes with selective type II atrophy. Sarcoplasmic/endoplasmic reticulum Ca2+ ATPase (SERCA) activity was reduced and western blot analysis showed decreased or absent SERCA1 protein. Based on this cohort, we conclude that Brody disease should be considered in cases of exercise-induced muscle stiffness. When physical examination shows delayed relaxation, and there are no myotonic discharges at electromyography, we recommend direct sequencing of the ATP2A1 gene or next generation sequencing with a myopathy panel. Aside from clinical features, SERCA activity measurement and SERCA1 western blot can assist in proving the pathogenicity of novel ATP2A1 mutations. Finally, patients with Brody disease may be at risk for malignant hyperthermia-like episodes, and therefore appropriate perioperative measures are recommended. This study will help improve understanding and recognition of Brody disease as a distinct myopathy in the broader field of calcium-related myopathies.

The goblet sign in the amnestic syndrome of the subcallosal artery infarct.

We here describe an acute-onset amnesic syndrome with evidence of an embolic infarction in the distribution of the subcallosal artery, a proximal branch of the anterior communicating artery. The infarction involved the corpus callosum genu and both fornices, giving a peculiar image on MRI that resembled a goblet. Although infrequent, the subcallosal artery infarction should be considered in the differential diagnosis of patients with an acute amnestic syndrome. We propose "the goblet sign" for the peculiar diffusion-weighted MRI image of the brain in this syndrome.

Alteraciones reversibles en los núcleos dentados y atrofia cerebral de rápida instauración debido a neurotoxicidad por litio / Reversible alterations in the dentate nuclei and rapid-onset cerebral atrophy due to neurotoxicity caused by lithium

Introducción. El tratamiento con litio puede ocasionar diversos efectos adversos neurológicos, incluso con niveles terapéuticos. Caso clínico. Mujer de 49 años, con trastorno bipolar y depresión, en tratamiento con litio, antidepresivos y antipsicóticos, que ingresó por un cuadro de alucinaciones visuales con una litemia elevada de 2,1 mEq/L (rango terapéutico: 0,6-1,2 mEq/L). Progresó a una encefalopatía grave que requirió asistencia respiratoria en la unidad de cuidados intensivos. La resonancia magnética cerebral inicial mostró una hiperintensidad simétrica bilateral reversible en los núcleos dentados en las secuencias T2 y T2-FLAIR. A lo largo de los meses posteriores desarrolló de forma progresiva un síndrome pancerebeloso con evidencia de una marcada pérdida de volumen bilateral en el cerebelo, sobre todo a expensas del vermis, que se acompañó clínicamente de un síndrome cerebeloso permanente e invalidante. Conclusiones. Aunque el tratamiento con litio ocasiona efectos adversos neurológicos variados, éstos suelen ser reversibles. Puede dar lugar a secuelas permanentes e incapacitantes, como la paciente descrita, con una atrofia cerebelosa marcada y progresiva, acompañada de secuelas permanentes en forma de síndrome cerebeloso invalidante. La neurotoxicidad cerebelosa del litio debe considerarse en el amplio diagnóstico diferencial que representa la ataxia cerebelosa del adulto (AU)

Introduction. Treatment with lithium can cause several neurological side effects, even at therapeutic levels. Case report. We report the case of a 49-year-old woman, with bipolar disorder and depression, undergoing treatment with lithium, antidepressants and antipsychotics, who was admitted to hospital due to a clinical picture of visual hallucinations with an elevated lithaemia of 2.1 mEq/L (therapeutic range: 0.6-1.2 mEq/L). The patient developed a severe encephalopathy that required the use of assisted ventilation in the intensive care unit. Initial magnetic resonance imaging showed a reversible bilateral symmetrical hyperintensity in the dentate nuclei in T2 and T2-FLAIR sequences. Over the following months she gradually developed a pancerebellar syndrome with evidence of a marked loss of bilateral volume in the cerebellum, above all at the expense of the vermis, which was accompanied by a permanent and disabling cerebellar syndrome. Conclusions. Although treatment with lithium can cause a variety of neurological side effects, they are usually reversible. However, they occasionally give rise to permanent and disabling sequelae, as in the case of the patient reported here, with a marked and progressive cerebellar atrophy, accompanied by permanent sequelae in the form of a disabling cerebellar syndrome. The cerebellar neurotoxicity of lithium must be taken into account in the broad differential diagnosis of cerebellar ataxia in adults (AU)

Influenza-associated seizures in healthy adults: Report of 3 cases.

To describe seizures occurring in 3 healthy adults with influenza infection. Seizures associated to influenza infection are rare in adults without encephalitis. Clinical observations of 3 healthy adult patients with influenza A and B infection and seizures. We present here 3 healthy adult patients with seizures related to influenza A or B infection without evidence encephalitis, encephalopathy or any other cause for seizures. Prognosis was excellent. Seizures can occur in healthy adults with influenza infection without evidence of encephalitis, a possibility to be borne in mind to avoid potentially harmful therapeutic and diagnostic procedures.

Novel mutations expand the clinical spectrum of DYNC1H1-associated spinal muscular atrophy.

OBJECTIVE: To expand the clinical phenotype of autosomal dominant congenital spinal muscular atrophy with lower extremity predominance (SMA-LED) due to mutations in the dynein, cytoplasmic 1, heavy chain 1 (DYNC1H1) gene. METHODS: Patients with a phenotype suggestive of a motor, non-length-dependent neuronopathy predominantly affecting the lower limbs were identified at participating neuromuscular centers and referred for targeted sequencing of DYNC1H1. RESULTS: We report a cohort of 30 cases of SMA-LED from 16 families, carrying mutations in the tail and motor domains of DYNC1H1, including 10 novel mutations. These patients are characterized by congenital or childhood-onset lower limb wasting and weakness frequently associated with cognitive impairment. The clinical severity is variable, ranging from generalized arthrogryposis and inability to ambulate to exclusive and mild lower limb weakness. In many individuals with cognitive impairment (9/30 had cognitive impairment) who underwent brain MRI, there was an underlying structural malformation resulting in polymicrogyric appearance. The lower limb muscle MRI shows a distinctive pattern suggestive of denervation characterized by sparing and relative hypertrophy of the adductor longus and semitendinosus muscles at the thigh level, and diffuse involvement with relative sparing of the anterior-medial muscles at the calf level. Proximal muscle histopathology did not always show classic neurogenic features. CONCLUSION: Our report expands the clinical spectrum of DYNC1H1-related SMA-LED to include generalized arthrogryposis. In addition, we report that the neurogenic peripheral pathology and the CNS neuronal migration defects are often associated, reinforcing the importance of DYNC1H1 in both central and peripheral neuronal functions.