The locked-in syndrome: The early French descriptions.

The classic 1966 description of locked-in syndrome was performed by Plum and Posner. Here, we revisit the world's first case report of this condition, which was presented in 1875 by Camille Darolles, an intern supervised by François Damaschino, at a monthly meeting of the Société Anatomique de Paris chaired by Jean-Martin Charcot. We also review the fascination of classic writers with this syndrome, including Alexandre Dumas, a genius of literature and known admirer of the medical sciences who, in the book "The Count of Monte Cristo" published in 1846, described a character with this condition.

Autonomic dysfunction in hereditary spastic paraplegia type 4.

BACKGROUND AND PURPOSE: SPAST mutations are the most common cause of hereditary spastic paraplegia (SPG4-HSP), which is characterized by progressive lower limb weakness, spasticity and hyperreflexia. There are few studies about non-motor manifestations in this disease and none about autonomic involvement. Therefore, the aim was to determine the frequency and pattern of autonomic complaints in patients with SPG4-HSP, as well as to determine the clinical relevance and the possible factors associated with these manifestations. METHODS: Thirty-four molecularly confirmed SPG4 patients were recruited in a multicenter cross-sectional study, of whom 26 underwent detailed neurophysiological testing (heart rate variability, sympathetic skin response and the Quantitative Sudomotor Axonal Reflex Test). The Scales for Outcomes in Parkinson's Disease - Autonomic Questionnaire (SCOPA-AUT) was applied to quantify the severity of autonomic symptoms. Results were compared with 44 age- and gender-matched healthy controls using non-parametric tests. P values <0.05 were considered significant. RESULTS: In the SPG4-HSP group, there were 18 men with a mean age of 47.7 ± 12.6 years. SCOPA-AUT scores were similar between patients and controls (P = 0.238). Only the urinary domain subscore was significantly higher amongst patients (4 vs. 2.5, P = 0.05). Absent sympathetic skin response in the hands and feet was more frequent amongst patients (20% vs. 0%, P < 0.001, and 64% vs. 0%, P = 0.006, respectively). Quantitative Sudomotor Axonal Reflex Test responses were also smaller throughout all recording regions in the SPG4-HSP group. CONCLUSION: Our results indicate that SPG4-HSP patients have sudomotor dysfunction caused by damaged small post-ganglionic cholinergic fibers. Damage in SPG4-HSP extends to the peripheral nervous system.

Consensus Paper: Neurophysiological Assessments of Ataxias in Daily Practice.

The purpose of this consensus paper is to review electrophysiological abnormalities and to provide a guideline of neurophysiological assessments in cerebellar ataxias. All authors agree that standard electrophysiological methods should be systematically applied in all cases of ataxia to reveal accompanying peripheral neuropathy, the involvement of the dorsal columns, pyramidal tracts and the brainstem. Electroencephalography should also be considered, although findings are frequently non-specific. Electrophysiology helps define the neuronal systems affected by the disease in an individual patient and to understand the phenotypes of the different types of ataxia on a more general level. As yet, there is no established electrophysiological measure which is sensitive and specific of cerebellar dysfunction in ataxias. The authors agree that cerebellar brain inhibition (CBI), which is based on a paired-pulse transcranial magnetic stimulation (TMS) paradigm assessing cerebellar-cortical connectivity, is likely a useful measure of cerebellar function. Although its role in the investigation and diagnoses of different types of ataxias is unclear, it will be of interest to study its utility in this type of conditions. The authors agree that detailed clinical examination reveals core features of ataxia (i.e., dysarthria, truncal, gait and limb ataxia, oculomotor dysfunction) and is sufficient for formulating a differential diagnosis. Clinical assessment of oculomotor function, especially saccades and the vestibulo-ocular reflex (VOR) which are most easily examined both at the bedside and with quantitative testing techniques, is of particular help for differential diagnosis in many cases. Pure clinical measures, however, are not sensitive enough to reveal minute fluctuations or early treatment response as most relevant for pre-clinical stages of disease which might be amenable to study in future intervention trials. The authors agree that quantitative measures of ataxia are desirable as biomarkers. Methods are discussed that allow quantification of ataxia in laboratory as well as in clinical and real-life settings, for instance at the patients' home. Future studies are needed to demonstrate their usefulness as biomarkers in pharmaceutical or rehabilitation trials.

Non-motor symptoms in patients with hereditary spastic paraplegia caused by SPG4 mutations.

BACKGROUND AND PURPOSE: Non-motor manifestations are frequently overlooked in degenerative disorders and little is known about their frequency and clinical relevance in SPG4 hereditary spastic paraplegia (SPG4-HSP). METHODS: Thirty patients with SPG4-HSP and 30 healthy controls answered the Modified Fatigue Impact Scale, Epworth Sleepiness Scale, Brief Pain Inventory and Beck Depression Inventory. Student's t test was used to compare groups and linear regression was used to assess correlations. RESULTS: Patients had higher fatigue scores than controls (31.0 ± 16.5 vs. 14.5 ± 16.0, P = 0.002) as well as pain (3.4 ± 2.7 vs. 1.0 ± 1.6, P = 0.001) and depression (12.7 ± 8.9 vs. 4.4 ± 3.8, P < 0.001, respectively). Fatigue was associated with depression and possibly with disease severity (P = 0.008 and 0.07, respectively). CONCLUSIONS: Fatigue, pain and depression are frequent and often severe manifestations in patients with SPG4-HSP.

Lean body mass: reference values for Italian population between 18 to 88 years old.

OBJECTIVE: Body's lean mass compartment is a strong predictor of morbidity and mortality risk in various clinical conditions. This paper proposes a simple and easily applied reference table for lean body mass (LBM) and lean body mass index (LBMI) for the Italian population. PATIENTS AND METHODS: Retrospective analysis of a database containing anthropometric and DXA body composition measurements obtained from a cross-sectional study conducted between 2002 and 2009 with Italian individuals. Parametric and nonparametric tests were performed using R 3.1.1 and SPSS 22.0 software packages. RESULTS: The 3712 study participants, 37.3% men and 62.7% women, aging from 18 to 88 years. Individuals with normal weight, overweight and obesity were evenly distributed in the sample. LBM and LBMI measures were significantly higher in males. In both genders, there was a significant and progressive decline in these measures associated with aging. Significant differences in LBMI between genders were found in all age groups except for individuals over 75 years. CONCLUSIONS: Based on the participants LBM profile, a reference table for LBM values was proposed. This reference will be useful to detect changes in the LBM compartment of individuals from the South Central Region of Italy, supporting health professionals during the process of diagnosing sarcopenia.

Central nervous system paracoccidioidomycosis: clinical features and laboratorial findings.

OBJECTIVE: To study prospectively the clinical features and laboratorial characteristics of 24 patients with central nervous system (CNS) involvement with paracoccidioidomycosis (PCM). PCM is an infectious disease caused by the dimorphic fungus Paracoccidioides brasiliensis, endemic in subtropical areas of Central and South America. METHODS: From 173 cases of PCM, 24 (13.9%) had CNS involvement (NPCM) and were studied prospectively from 1993 to 1997. In all the patients, the diagnosis of systemic PCM was made by the demonstration of the P. brasiliensis organisms or positive serology, DID (double immunodiffusion). In seven cases the diagnosis was made by means of a CNS biopsy. CNS clinical manifestations, neuroimaging (CT or MRI) and CSF cytochemical characteristics were reported. RESULTS: The mean age was 44 years (range 25-72 years); 23 patients were male, only one was female. Neurological symptoms began before systemic symptoms in 21%; simultaneously in 33%, and after systemic symptoms in 46%. Epilepsy was the more frequent neurological presentation (44%). Twenty-three cases had parenchymatous involvement and in two of these cases there was an association with meningitis and one case had spinal cord involvement. Lesions were more frequent in the brain hemispheres (69%), in 65% there were multiple granuloma characterized by hypodense images with annular or nodular enhancing. All cases were treated with sulphamethoxazole-trimethoprin. Four patients died, while 20 patients showed a good therapeutic response. CONCLUSION: NPCM should always be considered in the differential diagnosis of expanding lesions of the CNS and meningoencephalitis. Being alert to this diagnosis depends on knowledge of epidemiology. There was good response to sulphamethoxazole-trimethoprin treatment.

[Hereditary cerebellar ataxias: from hammer to genetics]. / Ataxias cerebelares hereditárias. Do martelo ao gen.

The hereditary ataxias comprise a complex group of neurological disorders involving the cerebellum and its connections. Several classifications based on clinical and/or pathological data have been only partially successful. Recent progress in molecular genetics has identified the genic loci of hereditary ataxias and has allowed a more precise diagnosis of distinct genetic diseases. Trinucleotide repeat expansions has been recognized as a mechanism of disease in some autosomal dominant spinocerebellar ataxias (ADCA) (SCA1 to SCA7), including Machado-Joseph disease/SCA3, probably the most common form of ADCA in South Brazil, and Friedreich ataxia (GAA expansion-chromosome 9p). Familial alpha-tocopherol deficiency (chromosome 8q) may have a Friedreich ataxia phenotype and responds to the oral supplementation with vitamin E. Familial episodic ataxias with (EA1-chromosome 12p) and without (chromosome 19p-EA2) myokimia were identified, the first one caused by point mutations in the gene encoding the KCNA1 potassium voltage-gated channel. The gene responsible for ataxia-teleangiectasia (chromosome 11q) was found to encode a putative DNA binding protein kinase (ATM), related to the cell cycle control. One to 3% of the population are heterozygotic ATM gen carry and pose a higher risk of cancer when exposed to ionizing radiation. Molecular biology has provided us with useful tools to diagnosis and genetic counseling and, hopefully, will provide us with a better understanding of the pathogenesis and eventual treatment of the several forms of hereditary ataxias.

Worsening of Parkinsonism after the use of veralipride for treatment of menopause: case report.

We describe a female patient with stable Parkinson's disease who has shown a marked worsening of her motor functions following therapy of menopause related symptoms with veralipride, as well as the improvement of her symptoms back to baseline after discontinuation of the drug. We emphasize the anti-dopaminergic effect of veralipride.

[Myasthenia gravis. Clinical and therapeutic evaluation of 55 cases]. / Miastenia grave. Avaliação clínica e terapêutica de 55 casos.

It is reported the study of 55 myasthenia gravis cases, with a review of the symptoms and signals, comparing initial symptoms ant those found at the time of the first evaluation. The mean age of the patients was 31.05 +/- 18.46 and the mean time of follow-up 5.88 +/- 5.47 years. Also the results of the diagnostic tests is reported, as well as the results of the treatment. The patients were treated with anticholinesterasics, corticosteroids, azathioprine, plasma-exchange and thymectomy. A statistical analysis with the chi-square test was unable to show a difference between the above procedures, regarding the definitive resolution of the disease. From the 55 cases, 9 (16.6%) had total remission, 41 (74.5%) remained with symptoms and need some kind of treatment, and 5 (9.09%) died (three patients with thymoma, one patient with congenital myasthenia gravis, severe kyphoscoliosis and pulmonary restriction, and one patient during the thymectomy procedure). It was found a relation between the signs of respiratory insufficiency, myasthenic crisis and thymoma only in the group of patients who died. A review about the diagnostic methods and treatment in the current days is made.

The Rolex sign: first manifestation of Parkinson's disease: case report.

We describe a patient whose initial manifestation of Parkinson's disease was a malfunctioning of a self-winding wristwatch secondary to bradykinesia of his left arm. Andrade and Ferraz reported this sign in 1996, suggesting that it be called the Rolex sign.

[Treatment of spasticity: an update]. / Tratamento da espasticidade. Uma atualização.

We present an update about the treatment of spasticity, stressing the pharmacological treatment, physical therapy and botulinum toxin therapy.

[Hemiballism: report of eight cases]. / Hemibalismo: relato de oito casos.

We report eight cases of hemiballism. Six patients had diabetes mellitus, one patient presented with porencephaly after cranial trauma and one patient had a HIV-associated fungic granuloma (cryptococcus). In the diabetic group three patients had non-ketotic hyperglycemia; two of them with striatal hemorrhage, and the remaining three presented with an ischemic stroke. Hemichorea occurred in 75% of our patients, predominantly in the right side of the body. Six patients had good improvement with treatment with haloperidol and two patients had to undergo a thalamotomy, one of them with good results. In our series of eight patients with hemiballismus we observed an association with diabetes mellitus and stroke, and good clinical improvement.

[Machado-Joseph disease: description of 5 members of a family]. / Doença de Machado-Joseph: descrição de cinco membros de uma família.

The authors report the clinical and laboratorial findings of 5 affected members (all males) of a family with Machado-Joseph disease. The mode a inheritance was autosomal dominant. The mean onset age was 38 years (range 30-50 years). The clinical picture was pleomorphic and included cerebellar ataxia, external ophthalmoplegia with bulging eyes, extrapyramidal/pyramidal syndromes, amyotrophy with fasciculations and peripheral neuropathy, in variable degrees of severity. In one patient parkinsonian rigidity was greatly improved with the use of trihexaphenidyl and L-dopa. CT scan examinations disclosed a variable degree of cerebellar atrophy, with mild cerebral atrophy in one patient. Brainstem evoked potentials were normal in two patients. EMG showed denervation in three patients. Muscle biopsy (gastrocnemium) with histochemical studies revealed chronic muscle denervation in four cases. Sural nerve biopsy with conventional pathological study was normal in four cases. This family was living in Florianopolis, Santa Catarina, where there is a great number of Portuguese descendants from the Azores Islands. The worldwide presence of the disease seems to result from the genic diffusion of the disease with the Portuguese emigration during the Great Navigations Era and with some later emigratory settlement.

Muscle involvement in leprosy. Study of the anterior tibial muscle in 40 patients.

The involvement of skeletal striated muscle in leprosy is considered secondary due to peripheral neuropathy, but some studies point it to a primary muscle lesion. In order to investigate the muscle involvement in leprosy, we studied 40 patients (lepromatous 23, tuberculoid 13, borderline 2 and indeterminate 2). The motor nerve conduction of the peroneal nerves had a reduction of the velocity, decreased compound muscle action potential and sometimes absence of potentials. The electromyographic study of the anterior tibial muscle showed signs of recent and chronic denervation in 77.5% of the cases and no myopathic potentials. The anterior tibial muscle biopsy revealed denervation in 45% of the cases, interstitial inflammatory myopathy in 30% and mixed (myopathic and neuropathic) pattern in 12.5%. Acid fast bacillus was detected in 25% of the cases, always in the interstitial tissue. Inflammatory reaction was present in the interstitial space and in patients with the lepromatous type. The histological findings clearly defined the presence of the so-called "Leprous Interstitial Myositis" on the top of denervation signs.

[Isaacs' syndrome. Report of three cases]. / Síndrome de Isaacs. Relato de três casos.

We report two females, and one male with Isaacs' syndrome. The patients presented with clinical myokymia activity, muscle cramps, delayed relaxation, and muscle hypertrophy and increased sweating. Needle electromyography in several muscles showed generalized continuous motor unit discharges, myokymic discharges, and normal nerve conduction studies. Muscle biopsy showed type two fiber atrophy. Treatment with carbamazepine was effective in two cases and prednisone in one.

[Dupuytren's and Ledderhose's diseases associated with chronic use of anticonvulsants. Case report]. / Doenças de Dupuytren e de Ledderhose associadas ao uso crônico de anticonvulsivantes. Relato de caso.

We present the case of a patient that after chronic use of anticonvulsant drugs without proven epilepsy, developed Dupuytren's and Ledderhose's diseases. We discuss the most frequent predisposing factors, and their relationship with chronic use of anticonvulsants, particularly phenobarbitone.