Volumetric MRI Changes in Spinocerebellar Ataxia (SCA3 and SCA10) Patients.

Spinocerebellar ataxias type 3 (SCA3) and type 10 (SCA10) are the most prevalent in southern Brazil. To analyze the relationships between volumetric MRI changes and clinical and genetic findings in SCA3 and SCA10 patients. All patients in the study had a confirmed genetic diagnosis. Demographic data, ataxia severity (SARA score), and the size of the expanded alleles were evaluated. Nineteen SCA3 and 18 SCA10 patients were selected and compared with a similar number of healthy controls. Patient and control groups underwent the same MRI protocol. The standard FreeSurfer pipeline was used for the morphometric data. Our results show more affected brain structures (volume reductions) in SCA3 patients than in SCA10 patients (15 vs. 5 structures). Volume reductions in brain structures were also greater in the former. The main areas with significant volumetric reductions in the former were the cerebellum, basal ganglia, brain stem, and diencephalon, whereas in the latter, significant volume reductions were observed in the cerebellum and pallidum. While SARA scores and disease duration were more correlated with volume reduction in SCA10, in SCA3, the expansion length (CAGn) correlated positively with cerebellar WM, thalamus, brain stem, and total GM volumes. There was no correlation between expansion length (ATTCTn) and neuroimaging findings in SCA10. Neuroimaging results differed significantly between SCA3 and SCA10 patients and were compatible with the differences in clinical presentation, disease progression, and molecular findings.

Higher latitude is significantly associated with an earlier age of disease onset in multiple sclerosis.

BACKGROUND: Age at onset (AAO) in multiple sclerosis (MS) is an important marker of disease severity and may have prognostic significance. Understanding what factors can influence AAO may shed light on the aetiology of this complex disease, and have applications in the diagnostic process. METHODS: The study cohort of 22 162 eligible patients from 21 countries was extracted from the MSBase registry. Only patients with MS aged ≥16 years were included. To reduce heterogeneity, only centres of largely European descent were included for analysis. AAO was defined as the year of the first symptom suggestive of inflammatory central nervous system demyelination. Predictors of AAO were evaluated by linear regression. RESULTS: Compared with those living in lower latitudes (19.0-39.9°), onset of symptoms was 1.9 years earlier for those at higher latitudes (50.0-56.0°) (p=3.83×10-23). A reciprocal relationship was seen for ambient ultraviolet radiation (UVR), with a significantly increasing AAO for patients with MS per each quartile increment of ambient UVR (p=1.56×10-17). We found that the AAO of female patients was ∼5 months earlier than male patients (p=0.002). AAO of progressive-onset patients with MS were ∼9 years later than relapsing-onset patients (p=1.40×10-265). CONCLUSIONS: An earlier AAO in higher latitude regions was found in this worldwide European-descent cohort and correlated inversely with variation in latitudinal UVR. These results suggest that environmental factors which act at the population level may significantly influence disease severity characteristics in genetically susceptible populations.

Analysis of diffusion tensor parameters in spinocerebellar ataxia type 3 and type 10 patients.

INTRODUCTION: There is a dearth of studies of spinocerebellar ataxias (SCAs) and diffusion tensor magnetic resonance imaging (DTI). OBJECTIVE: To analyze changes observed in DTI parameters and correlate these to clinical findings in SCA3 and SCA10 patients. METHODS: SCA3 (n = 19) and SCA10 (n = 18) patients were compared with a similar number of controls and assessed clinically and with the scale for the assessment and rating of ataxia (SARA) before undergoing the same MRI protocol. TRACULA (TRActs Constrained by UnderLying Anatomy) software was used to analyze the DTI metrics FA, AD, RD and MD. RESULTS: More white matter fiber tracts with changes in diffusivity were found in SCA3 patients than in SCA10 patients. There was a reduction in AD in altered fiber tracts in SCA3 and a greater increase in RD in SCA10. In the SCA3 patients, FA was reduced in the corticospinal tract (CST) and inferior longitudinal fasciculus (ILF), but this was not observed in the SCA10 patients. SARA score was correlated with DTI findings in SCA3 but not in SCA10. CONCLUSION: Changes were observed in DTI for both SCA3 and SCA10 but were more widespread in SCA3. Our finding of myelin-sheath changes in SCA10 and secondary axonal changes in SCA3 may reflect the more rapid, aggressive clinical course of SCA3.

Neuroradiological Findings in the Spinocerebellar Ataxias.

Background: The spinocerebellar ataxias (SCAs) are a group of autosomal dominant degenerative diseases characterized by cerebellar ataxia. Classified according to gene discovery, specific features of the SCAs - clinical, laboratorial, and neuroradiological (NR) - can facilitate establishing the diagnosis. The purpose of this study was to review the particular NR abnormalities in the main SCAs. Methods: We conducted a literature search on this topic. Results: The main NR characteristics of brain imaging (magnetic resonance imaging or computerized tomography) in SCAs were: (1) pure cerebellar atrophy; (2) cerebellar atrophy with other findings (e.g., pontine, olivopontocerebellar, spinal, cortical, or subcortical atrophy; "hot cross bun sign", and demyelinating lesions); (3) selective cerebellar atrophy; (4) no cerebellar atrophy. Discussion: The main NR abnormalities in the commonest SCAs, are not pathognomonic of any specific genotype, but can be helpful in limiting the diagnostic options. We are progressing to a better understanding of the SCAs, not only genetically, but also pathologically; NR is helpful in the challenge of diagnosing the specific genotype of SCA.

Alternative option for osteogenesis imperfecta and trigeminal neuralgia.

Osteogenesis imperfecta (OI) is a bone disorder that can lead to skull base deformities such as basilar invagination, which can cause compression of cranial nerves, including the trigeminal nerve. Trigeminal neuralgia in such cases remains a challenge, given distorted anatomy and deformities. We present an alternative option, consisting in cannulation of the foramen ovale and classical percutaneous treatment. Percutaneous balloon microcompression was performed in a 28 year-old woman with OI and severe trigeminal neuralgia using computed tomography (CT) and radiographic-guided cannulation of the Gasserian ganglion without neuronavigation or stereotactic devices. The patient developed hypoesthesia on the left V1, V2 and V3 segments with good pain control. This alternative technique with a CT-guided puncture, using angiosuite without the need of any Mayfield clamp, neuronavigation systems, frame or frameless stereotactic devices can be a useful, safe and efficient alternative for patients with trigeminal neuralgia with other bone deforming diseases that severely affect the skull base.

No correlation was observed between vitamin D levels and disability of patients with multiple sclerosis between latitudes 18° and 30° South.

Objective: Vitamin D has taken center stage in research and treatment of multiple sclerosis (MS). The objective of the present study was to assess the serum vitamin D levels of a large population of patients with MS and controls living in a restricted tropical area. Methods: Data from 535 patients with MS and 350 control subjects were obtained from 14 cities around the Tropic of Capricorn. Results: The mean serum 25-OH vitamin D level was 26.07 ± 10.27 ng/mL for the control subjects, and 28.03 ± 12.19 ng/mL for patients with MS. No correlation was observed between vitamin D levels and the disability of patients over the disease duration. Conclusion: At least for the region around the Tropic of Capricorn, serum levels of vitamin D typically are within the range of 20 to 30 ng/mL for controls and patients with MS.

[Neurophysiological study in slow-channel congenital myasthenic syndrome: case report]. / Estudo neurofisiológico na síndrome miastênica congênita do canal lento: relato de caso.

The slow-channel syndrome is one of the congenital myasthenic syndromes attributed to inherited kinetic disorders of the ion channel of the acetylcholine receptor of the neuromuscular junction. This is a case report of 25-years-old man with progressive ptosis and limitation of ocular movements since infancy, presented a 6-years history of worse of the external ophthalmoparesis and muscular weakness in the shoulders and hands. The motor nerve conduction studies after a supramaximal single stimulus disclosed a double compound muscle action potential (CMAP) that disappeared after a voluntary contraction of 30 seconds. Repetitive stimulation of facial and spinal accessory nerves showed a CMAP decrement greater than 10% with disappeared of the second potential. The patient received fluoxetine with mild improvement of muscular weakness, but persisted with: ptosis, limitation of ocular movements and repetitive CMAP in the motor nerve conduction study. The characteristic of disease are discussed.

[Foix-Alajouanine syndrome: case report].

In a 52-year-old woman, spinal arteriovenous malformation (AVM) has been associated with what has been known as Foix-Alajouanine syndrome. The pathophysiology of the AV fistula is probably related to increased venous pressure from the AVM plus thrombotic process. The most common initial symptoms are sensory disturbance, pain and leg weakness. Definitive diagnosis of spinal AVMs requires radiographic demonstration of the vascular anomaly. Nevertheless, in this case, suggestive defects of malformations could not be seen, in contrast to the MRI findings and macroscopical and anatomical-pathological lesion. These findings rise our attention, about the need to keep in mind the clinical suspicion of AVM in cases of back pain and motor deficit, and an early surgical conduct in this situation.

Intrinsic tectal low grade astrocytomas: is surgical removal an alternative treatment? Long-term outcome of eight cases.

Low-grade gliomas arising in dorsal midbrain in children and young patients usually present few neurological symptoms and findings, and patients management is controversial. Some authors propose only clinical observation until the patient present signs of increased intracranial pressure when a shunt with or without biopsy, is inserted; others recommend radiotherapy after stereotactic or open biopsy. Microsurgical total removal of tumor may be curative. We present a retrospective analysis of eight patients (mean age 16.6 +/- 11.5 years-old) with low-grade astrocytoma of the tectal region operated on using an infratentorial/supracerebellar approach between 1981 and 2002. All patients presented hydrocephalus and had a shunt insertion before surgical resection of the lesion. The tumour could be totally resected in seven patients. In one case radical removal was not possible due to infiltrative pattern of the lesion. Postoperative radiotherapy was performed in two cases, one patient at the beginning of this series and in the case with infiltrative tumor. This patient presented progressive tumor growth and died five years after surgery. No recurrence occurred after total removal. Post-surgical follow-up time ranged from 2 1/2 to 22 1/2 years (mean 9.9 +/- 5.9 years). Radical microsurgical removal of non invasive tumors is possible without mortality or significant morbidity. It may be curative and should remain as an alternative to be discussed with the patient.

Mitoxantrone in secondarily progressive multiple sclerosis: a series of 18 patients.

Mitoxantrone hydrochloride (Novantrone) is an anthracenedione that has been used as one of the latest in a long line of general immunosuppresive agents studied in multiple sclerosis (MS). We reviewed the clinical, laboratory, neuroimaging and echocardiography data of 18 patients from February 2001 to March 2004 out of a total number of 100 patients with definite MS. Fourteen patients were women (77.7%) and four were men. The mean age of the patients was 41.6 +/- 10 years old (confidence intervals 95%: 36.4-46.7 years old). The mean duration of disease was 10.5 +/- 6.3 years. Fourteen patients had the secondarily progressive form of MS, and four had the relapsing-remitting form. Mitoxantrone is an useful and clinically effective drug in MS and its major limitation is the potencial cardiotoxicity due to cumulative dose (140 mg).

Acute myeloid leukaemia induced by mitoxantrone: case report.

Mitoxantrone (MX) is an immunosupressant drug used in secondarily progressive multiple sclerosis (SPMS) and in relapsing-remitting multiple sclerosis (RRMS). It has a leukemogenesis potential induced by cytogenetic abnormalities, though with a low incidence. Promyelocitic leukaemia (type M3) and other forms of acute myeloblastic leukaemias (M4 and M5) have been described in a few MS patients who received MX during their treatment. We describe a white female patient, 47 year-old, with SPMS (EDSS = 4) with 14 years of disease. She received MX during her disease and developed acute promyelocytic leukaemia (M3), with severe thrombocytopenia 30 months later. She ultimately died due to intracerebral hemorrhage. Other cases of treatment related to AML are reviewed and discussed.

Syncope or epileptic fits? Some examples of diagnostic confounding factors.

Syncope is a condition often misdiagnosed as epileptic seizures. However, the differential diagnosis between both conditions can be quite difficult, even for well-trained physicians. Four cases of epilepsy and/or syncope are reported, to exemplify this situation. Each case is discussed individually, and the confounding factors are analyzed.

CT scan findings in mild head trauma: a series of 2,000 patients.

The present study describes the cranial computed tomography (CT) scan findings of 2,000 cases of mild head trauma (HT) in Curitiba, Southern Brazil. The mean age of the entire series was 30.8 +/-19 years. The overall male to female ratio was 2:1. The most common causes of head injury were interpersonal aggression (17.9%), falls (17.4%), automobile accidents (16.2%), falls to the ground (13.1%) and pedestrian injuries (13 %). Alcohol intoxication was associated with HT in 158 cases (7.9%). A normal CT scan was seen in 60.75% (1215) and an abnormal CT scan in 39.25% (785) of patients. Out of 785 abnormal CT scan, 518(65.9%) lesions were related to HT. The most common CT scan HT related findings were: soft tissue swelling (8.9 %), skull fractures (4.3 %), intracranial and subgaleal hematomas (3.4% and 2.4 %), brain swelling (2 %) and brain contusion (1.2%). Out of 785 abnormal CT scans, 267 (34.1%) lesions were not related to head trauma. Incidental CT scan findings included brain atrophy (5.9%), one calcification (5.2%) several calcifications (2.4%) (probably neurocysticercosis in most cases), ischemic infarct (1.9%) and leukoaraiosis (1.3%). These findings showed the importance of CT scan examination in mild head injuries. Further studies to identify mild HT patients at higher risk of significant brain injury are warranted in order to optimize its use.

[The Drew family of Walworth: one century from the first evaluation until the final diagnosis, Machado-Joseph disease]. / A família Drew de Walworth--um século após a avaliação inicial finalmente o diagnóstico: doença de Machado-Joseph.

Autosomal dominant spinocerebellar ataxia (SCA) is an heterogeneous group of neurodegenerative diseases involving cerebellum and its connections. Several forms have already been described, and it seems the most common form of SCA observed among the many series of families described worldwide is SCA3 (Machado-Joseph disease). SCA3 is characterized by a marked phenotypic expression with a wide spectrum of clinical findings including cerebellar ataxia, pyramidal and extrapyramidal (e.g. dystonia, parkinsonism), lower motor neuron syndrome and peripheral neuropathy. The Drew family of Walworth, England, has several affected members seen and described by famous neurologists including Gowers, Stewart, Collier, Kinnier-Wilson, Turner, Worster-Drought, Ferguson, Critchley, and Anita Harding from 1895 to our days. In fact, the final genetic diagnosis of this family, 100 years after its initial description, turned out to be SCA3. In this paper, we describe the full of twists and turns historical trajectory from the initial clinical description to the final genetic diagnosis.

[Creutzfeldt-Jakob disease, Heidenhain variant: case report with MRI (DWI) findings]. / Doença de Creutzfeldt-Jakob forma Heidenhain: relato de caso com achados de ressonância magnética e DWI.

Creutzfeldt-Jakob disease (CJD) is a presenile dementia characterized by rapidly progressive mental deterioration, myoclonic jerking, and other less common neurological signs. Few autoctonous cases have been described in Brazil. A 54-year-old white woman, was admitted in our service with a month history of progressive, bilateral cortical blindness. After admission, she developed right partial motor seizures( right facial, upper and lower limbs), she became progressively aphasic( mixed aphasia). Seizures were controlled with phenytoin, but she developed choreoathetotic movements on her right dimidium, with partial control after introduction of chlorpromazine 25 mg q/d. She could no longer stand up or walk due to severe ataxia. The first EEG (October, 2001) showed left hemisphere severe seizure activity (status epilepticus partialis). She was delivered home with enteral nutrition, phenytoin, chlorpromazine and mepacrine 100 mg qd. The following laboratorial tests were negative or normal: blood series, platelets, ESR, kidney and liver function, copper, ceruloplasmin, VDRL, HIV, HTLV-1, lactate, and cerebral DSA (performed in other service).A spinal tap with normal opening pressure was perform and CSF examination was normal. CSF 14-3-3 protein was positive, CSF specific neuronal enolase 7.5 ng/ml(normal). Genetic study of PRNP gene did not disclosed any known mutation. A MRI (October, 2001) showed areas of hyperintense signal (T2 and FLAIR) without Gd-enhancement on T1, in the left temporal lobe and in both occipital lobes; basal ganglia have a normal appearance. DWI imaging showed bright areas at the same sites. An EEG (March, 2002) disclosed a periodical sharp triphasic waves pattern, suggestive of CJD. A second MRI (April, 2002) showed mild generalized atrophy, no ventricular dilatation, and the hyperintense sites disappeared. She remained clinically stable and under use of chlorpromazine and mepacrine until she died due to pulmonary complications on April, 2003.

Ankylosing spondylitis and central core disease: case report.

Ankylosing spondylitis (AS) is an inflammatory disorder of unknown cause that primarily affects the axial skeleton. Neurological manifestations of AS are usually related to spinal deformities. Previous studies of the paraspinal muscles of AS patients showed muscle fiber atrophy, and core fibers. On the other hand, central core disease (CCD) is a genetic condition that primarily involves the skeletal muscles, but can present articular deformities secondary to muscular weakness. We report the case of a 45-year-old man with clinical and radiological diagnosis of AS and proximal muscular weakness in the lower limbs. Needle electromyography showed myopathic features and nerve conduction study was normal. Muscle biopsy disclosed almost complete predominance of type-1 fibers, and fibers with central cores. This is the first report of AS and CCD. Whether central core myopathy is coincidental or a new association with AS is discussed.

Peritoneal dissemination from central neurocytoma: case report.

OBJECTIVE: Central neurocytoma is a low grade tumor of neuroglial origin and a relatively new histological entity. Only a few cases have been reported and its biological behavior is still uncertain. Some cases have shown an aggressive behavior (local recurrence, malignant dedifferentiation or CSF dissemination) and challenged the initial view of its relative benignity. A case of central neurocytoma with peritoneal dissemination is presented. CASE: A six years-old boy with recurrent neurocytoma of III ventricle and left thalamus showed fast growth of tumor rest and ascites three and a half years after subtotal removal of the lesion. Tumor cells were identified in the ascitic fluid and implanted in the peritoneum. Chemotherapy was initiated immediately after diagnosis of peritoneal dissemination (etoposide, carboplatin, doxorubicin and cyclophosphamide). The patient developed metabolic imbalance and respiratory failure due to rapid formation of ascitic fluid and died 3 days after the diagnosis of peritoneal dissemination was established. CONCLUSION: Central neurocytoma is a low grade tumor with low values of the proliferative index in the majority of cases. In spite of that, some tumors may present a very aggressive behavior and extraneural dissemination. Evaluation of proliferative index may be a guideline parameter for planning adjuvant therapies after surgical treatment in selected cases. Extraneural dissemination may occur in some cases specially in patients with ventriculoperitoneal shunt.

[Cerebral and systemic venous thrombosis associated to prothrombin G20210 mutation: case report]. / Trombose de seio venoso cerebral e trombose sistêmica associadas à mutação do gene 20210 da protrombina: relato de caso.

Cerebral venous thrombosis is a clinical condition of difficult diagnosis, and poor prognosis when treatment is not started early. There is a long list of causes, and hereby we describe a case associated to prothrombin G20210 mutation. A 53-year-old man, white, was admitted with status epilepticus. After seizures control, he developed intracranial hypertension, with headache and vomiting, and bilateral papilledema. His past medical and familial history were unremarkable. He was a nonsmoker, no drug and alcohol user. CT scan and MRI showed right temporal and parietal infarct with hemorrhagic transformation. Spinal tap with opening pressure of 500 mmH2O showed normal CSF examination. MRI angiography disclosed superior sinus, right transverse and sigmoid sinus complete thrombosis. He was started with heparin and oral warfarin. In spite of anticoagulation, two months later he developed deep right inferior limb thrombosis. All the initial tests were normal, and test for prothrombin G20210 mutation was positive. He needed a much higher than conventional daily dose of warfarin to keep him asymptomatic.

Myotonia congenita and myoadenylate deaminase deficiency: case report.

Approximately 1-2% of the population has a deficiency of the enzyme myoadenylate deaminase. Early reports suggested that patients with myoadenylate deaminase deficiency had various forms of myalgia, and exercise intolerance. However, a deficiency of the enzyme has been described in many conditions, including myopathies, neuropathies, and motor neuron disease. We report a patient with clinical diagnosis of myotonia congenita and absent myoadenylate deaminase reaction on the muscle biopsy. This is the first description of myoadenilate deaminase deficiency with myotonia congenita. Myoadenylate deaminase deficiency is the most common enzymatic deficit of muscle, and the association with other neuromuscular diseases is coincidental.