Clinical, biochemical, molecular, and histological features of 65 Portuguese patients with mitochondrial disorders.

INTRODUCTION: Mitochondrial disorders display remarkable genetic and phenotypic heterogeneity. METHODS: We performed a retrospective analysis of the clinical, histological, biochemical, and genetic features of 65 patients with molecular diagnoses of mitochondrial disorders. RESULTS: The most common genetic diagnosis was a single large-scale mitochondrial DNA (mtDNA) deletion (41.5%), and the most frequent clinical phenotype was chronic progressive external ophthalmoplegia (CPEO). It occurred in 41.5% of all patients, primarily in those with mtDNA deletions. Histological signs of mitochondrial dysfunction were found in 73.8% of patients, and respiratory chain enzyme assay (RCEA) abnormalities were detected in 51.9%. CONCLUSIONS: This study confirms the high relative frequency of single large-scale deletions among mitochondrial disorders as well as its particular association with CPEO. Muscle histology seems to be particularly useful in older patients and those with mtDNA deletions, whereas RCEA might be more helpful in young children or individuals with mtDNA depletion. Muscle Nerve 56: 868-872, 2017.

Dyschromatopsia in Multiple Sclerosis Patients: A Marker of Subclinical Involvement?

BACKGROUND: In multiple sclerosis (MS), even in the absence of a clinical episode of optic neuritis (ON), the optic nerve and retinal nerve fiber layer (RNFL) may be damaged leading to dyschromatopsia. Subclinical dyschromatopsia has been described in MS associated with lower motor and cognitive performances. OBJECTIVES: To set the prevalence of dyschromatopsia in eyes of MS patients without a history of ON, to compare its prevalence in patients with and without ON history, and to explore the association between dyschromatopsia and disease duration, average peripapillary RNFL thickness, macular volume, and cognitive and motor performances. METHODS: An observational cross-sectional study was conducted at multiple medical centers. Data were collected after single neurological and ophthalmological evaluations. Dyschromatopsia was defined by the presence of at least 1 error using Hardy-Rand-Rittler plates. RESULTS: In our population of 125 patients, 79 patients (63.2%) never had ON and 35 (28.8%) had unilateral ON. The prevalence of dyschromatopsia in eyes of patients without ON was 25.7%. Patients with dyschromatopsia had a statistically significant lower RNFL thickness (P = 0.004 and P = 0.040, right and left eyes, respectively) and worse performance in symbol digit modalities test (P = 0.012). No differences were found in macular volume or motor function tasks. CONCLUSIONS: Dyschromatopsia occurs frequently in MS patients. It may be associated with a worse disease status and possibly serve as a marker for the detection of subclinical disease progression since it was detected even in the absence of ON. It correlated with thinner peripapillary RNFL thickness and inferior cognitive performance.

Chronic Inflammatory Demyelinating Polyradiculoneuropathy and Diabetes: A Case Report.

We present a case of a 42-year-old female living with poorly controlled diabetes who presented with a nine-month evolution of ataxic gait, reduced motor and sensitive function of lower and upper limbs, and postural anesthesia of fingers, feet, and toes. Deep tendon reflexes were abolished in the lower limbs and markedly diminished in the upper limbs. Cerebrospinal fluid (CSF) analysis showed a high protein level, and both imaging and serologic studies were normal. Although she had a previous electrophysiologic study showing distal symmetric polyneuropathy (DSPN) with an axonal lesion, nerve conduction studies were repeated, and a diagnosis of chronic inflammatory demyelinating polyneuroradiculopathy (CIDP) was made. According to the state of the art, intravenous immunoglobulin (IVIg) was started. The patient's Inflammatory Neuropathy Cause and Treatment (INCAT) score and Medical Research Council (MRC) Sum Score both improved after two cycles. Unfortunately, symptoms quickly recurred, and corticosteroids were introduced to try to delay symptom recurrence, although it worsened diabetes control. Later, IVIg was stopped due to nephrotic syndrome, and immunosuppression was initiated. CIDP is a potentially treatable disease, but the diagnosis must be made as soon as possible to start therapy and reduce sequelae. Neuropathy in patients living with diabetes is common, but patients must be monitored closely to enable a correct diagnosis and adequate treatment.

Stiff person spectrum disorders: An illustrative case series of their phenotypic and antibody diversity.

Stiff person spectrum disorders (SPSD) are a broad group of immune-mediated disorders. Clinical presentations include classical stiff person syndrome (SPS), focal SPS, and progressive encephalomyelitis with rigidity and myoclonus (PERM). The most frequently associated antibodies are anti-GAD65, anti-GlyR, anti-amphiphysin, and anti-DPPX. Immunotherapy is the primary treatment modality. We present an illustrative case series of three patients: anti-GlyR antibody-mediated PERM presenting as rapidly progressive dementia; anti-amphiphysin antibody-mediated SPS; and SPS presentation with anti-Zic4 antibodies, spasmodic laryngeal stridor and fluctuating eyelid ptosis. Clinical characteristics, CSF findings, neurophysiological features, adequate immunological assays and a high suspicion index are essential for prompt diagnosis and management.

DOK7 myasthenic syndrome with subacute adult onset during pregnancy and partial response to fluoxetine.

DOK7 congenital myasthenic syndrome (DOK7-CMS) generally presents early in life and is treated with salbutamol or ephedrine. This report describes an atypical case of a 39-year-old woman who presented with proximal upper limb weakness in the third trimester of pregnancy and was initially diagnosed with seronegative myasthenia gravis. Dramatic clinical worsening under pyridostigmine and further inefficacy of steroids, intravenous human immunoglobulin (IVIG) and plasma exchange (PLEX) led to the presumptive diagnosis of a CMS. Initially, a slow-channel CMS was regarded as more probable due to prominent finger extension weakness. Accordingly, fluoxetine was started and a lengthy improvement was seen. Clinical deterioration occurred after fluoxetine withdrawal, when a c.1124_1127dup homozygous mutation was detected in DOK7 gene. Afterwards, salbutamol was started and the patient became asymptomatic. This case highlights the importance of considering CMS before an adult-onset myasthenic syndrome and suggests a benefit from fluoxetine not previously reported in DOK7-CMS.

A Case Report of Nonvasculitic Autoimmune Inflammatory Meningoencephalitis with Sensory Ganglionopathy: A Rare Presentation of Sjögren Syndrome.

A 68-year-old Caucasian female was admitted to the emergency department with a progressive history of behavioural symptoms and anxiety followed by visual and auditory hallucinations, forgetfulness, and impaired gait in the previous 3 months. On examination she was psychotic and had a postural and rest tremor of the upper limbs, cogwheel rigidity of the four limbs, retropulsion on standing position, and inability to walk. During the following 2 weeks she developed xerostomia and unilateral parotiditis that improved with steroids. A simultaneous improvement of the cognitive abilities allowed for the detection of sensory ataxia of the lower limbs. Sensory ganglionopathy was then detected with electrophysiological studies. A diagnosis of Sjögren syndrome was suspected and confirmed by salivary gland scintigraphy, Schirmer's test, and submaxillary gland biopsy. We report a case of Sjögren syndrome associated with central and peripheral nervous system involvement, without sicca symptoms preceding the neurological clinical picture. The coexistence of ganglionopathy and a favourable response to immunosuppression are key features that can lead to the correct diagnosis in cases with atypical CNS symptoms, mimicking a rapidly progressive dementia.

Bethlem Myopathy Phenotypes and Follow Up: Description of 8 Patients at the Mildest End of the Spectrum.

The classical phenotypes of collagen VI-associated myopathies are well described. Little is known, however, about the progression of patients at the mildest end of the clinical spectrum. In this report, we describe the clinical findings and the results of MRI, muscle biopsy, collagen VI expression in cultured skin fibroblasts and genetic tests of a series of patients with Bethlem myopathy. Our series highlights the existence of mild presentations of this disorder that progresses only slightly and can easily be overlooked. Analysis of the genetic studies suggests that missense mutations can be associated to a milder clinical presentation. Muscle MRI is extremely useful as it shows a pathognomonic pattern in most patients, especially those with some degree of muscle weakness.

Familial aggregation of cluster headache.

UNLABELLED: Several studies suggest a strong familial aggregation for cluster headache (CH), but so far none of them have included subjects with probable cluster headache (PCH) in accordance with the International Classification of Headache Disorders. OBJECTIVE: To identify cases of probable cluster headache and to assess the familial aggregation of cluster headache by including these subjects. METHOD: Thirty-six patients attending a headache consultation and diagnosed with trigeminal autonomic headaches were subjected to a questionnaire-based interview. A telephone interview was also applied to all the relatives who were pointed out as possibly affected as well as to some of the remaining relatives. RESULTS: Twenty-four probands fulfilled the criteria for CH or PCH; they had 142 first-degree relatives, of whom five were found to have CH or PCH, including one case of CH sine headache. The risk for first-degree relatives was observed to be increased by 35- to 46-fold. CONCLUSION: Our results suggest a familial aggregation of cluster headache in the Portuguese population.

[Multiple sclerosis: social and economic implications]. / Esclerose múltipla: implicações sócio-económicas.

Multiple Sclerosis (MS) is the most common demyelinating disease of the Central Nervous System. It is more frequently diagnosed in young individuals between 20 and 40 years old. MS is the leading non-traumatic cause for disability in young adults in western countries. Portuguese prevalence of the disease is about 50 per 100,000 inhabitants, which means that there are around 5,000 people with MS in Portugal. Our goal was to determine social and economic implications of MS through the description of patient's quality of life and economic difficulties, and to assess the dividend spent by the National Health System (NHS) with this disease. The studied population consisted of 50 individuals with MS in any stage of the disease to whom no exclusion criteria were used. The following questionnaires were applied: Multiple Sclerosis: Socio-Economic Implications and MS and Quality of Life (MSQoL-54). For data processing purposes we used SPSS v.16 and Microsoft Excel 2003. The confidence interval was 95%. In addition we based the cost calculations on K and C constants (official values from 2002). The results obtained were similar to those described in literature in what concerns the clinical presentation and the onset of the disease. Social implications evaluated by MSQoL revealed the majority of the inquiries had a score above 50 (n = 31). In what concerns economic implications the value of 40 843 250 euro was obtained as the mínimum spent by NHS. This number probably represents an under-valorization of the real value since only the direct costs were analyzed. It is necessary that new studies especially with bigger study populations can determine precisely the economic impact of MS in the Portuguese society.

Familial aggregation of cluster headache / Agregacao familiar da cefaleia em salvas

Several studies suggest a strong familial aggregation for cluster headache (CH), but so far none of them have included subjects with probable cluster headache (PCH) in accordance with the International Classification of Headache Disorders. Objective To identify cases of probable cluster headache and to assess the familial aggregation of cluster headache by including these subjects. Method Thirty-six patients attending a headache consultation and diagnosed with trigeminal autonomic headaches were subjected to a questionnaire-based interview. A telephone interview was also applied to all the relatives who were pointed out as possibly affected as well as to some of the remaining relatives. Results Twenty-four probands fulfilled the criteria for CH or PCH; they had 142 first-degree relatives, of whom five were found to have CH or PCH, including one case of CH sine headache. The risk for first-degree relatives was observed to be increased by 35- to 46-fold. Conclusion Our results suggest a familial aggregation of cluster headache in the Portuguese population. .

Diversos artigos sugerem uma significativa agregação familiar da cefaleia em salvas (CH) embora nenhum tenha incluído indivíduos com provável cefaleia em salvas (PCH), segundo critérios da Classificação Internacional de Cefaleias (ICHD-II). Objetivo Encontrar casos de provável cefaleia em salvas e avaliar a agregação familiar da cefaleia em salvas incluindo também esses indivíduos. Método Foi aplicado um questionário por telefone a 36 doentes que frequentaram uma Consulta de Cefaleias com diagnóstico de cefaleia trigémino-autonómica. Todos os familiares de primeiro grau referidos como possivelmente afetados e alguns dos restantes foram entrevistados por telefone. Resultados Em 24 doentes foi diagnosticada CH ou PCH e estes tinham 142 familiares de primeiro grau, cinco dos quais foram diagnosticados como CH ou PCH, incluindo um caso de CH sem cefaleias. O risco para familiares de primeiro grau foi 35-46 vezes superior ao da população geral. Conclusão Nossos resultados sugerem a existência de uma agregação familiar da cefaleia em salvas na população portuguesa. .

Disección de la arteria vertebral asociada a síndrome MURCS / Vertebral artery dissection associated with MURCS syndrome

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