Biomedical subjects
Publications and source records attributed to M J Rosas.
Sensory ataxia with neuropathy, dysarthria and ophthalmoparesis represent the clinical triad of SANDO, a specific mitochondrial phenotype first reported in 1997 in association with multiple mitochondrial DNA deletions and mutations in POLG1 or more rarely in the C10orf2 (twinkle-helicase) gene. We report a 44-year-old man with SANDO who harboured two novel mutations (P648R/R807C) in the POLG1 gene.
Factors influencing early hospital admission have been described for several stroke types but not for cerebral vein and dural sinus thrombosis (CVT). CVT is more difficult to diagnose than arterial stroke; delay in hospital admission may postpone CVT treatment. The purposes of this study were: (1) to describe the delay between the onset of symptoms and hospital admission of patients with CVT, and (2) to identify the variables that influence that delay. We registered the interval (days) between the onset of symptoms and hospital admission in 91 consecutive patients admitted to 20 Portuguese hospitals between June 1995 and June 1998. We also studied the impact of admission delay on treatments (prescription of anticoagulants and the number of days elapsed between the onset of symptoms and start of anticoagulation and admission). Median admission delay was 4 days. Twenty-two (25%) patients were admitted within 24 h. Two thirds of the patients were admitted within 7 days and 75% within 13 days. In multiple logistic regression analysis, admission within 24 h was positively associated with mental status disorder (delirium or abulia; OR = 4.59; 95% CI = 1.41-14.89) and negatively associated with headache (OR = 0.03; 95% CI = 0.00-0.32). Presentation as isolated intracranial hypertension was associated with admission delay of more than 4 days (OR = 2.63; 95% CI = 0.97-7.14). Papilloedema was associated with an admission delay of more than 13 days (OR = 4.69; 95% CI = 1.61-13.61). There was no association between admission delay and the proportion of anticoagulated patients. The interval between onset of symptoms and start of anticoagulation was shorter in patients admitted earlier (p = 0.0001, for either admission within 24 h, 4 or 13 days). There is a considerable delay until the clinical picture associated with CVT is recognised as justifying hospital admission, especially when patients present with symptoms identical to isolated intracranial hypertension syndrome.
To describe early symptomatic and late seizures in a cohort of patients with acute cerebral vein and dural sinus thrombosis (CVDST) and to identify their determinants, we performed a prospective registry and follow-up study of CVDST patients admitted to 20 Portuguese hospitals, from June 1995 to June 1998. Of 91 registered patients, 31 (34%) had early symptomatic seizures; 29 (31.9%) as a presenting feature and 2 (2.1%) after admission. Early symptomatic seizures were more frequent in patients with motor and sensory deficits and in those with focal oedema/ischaemic infarcts or haemorrhages on admission CT/MR. On multivariate logistic regression analysis, sensory defects (OR = 7.8; 95% CI = 0.8-74.8) and a parenchymal lesion on admission CT/MR (OR = 3.7, 95% CI = 1.4-9.4) were found to be significant predictors of early symptomatic seizures. Seizures were directly related to acute death in 2 patients. Eight (9.5%) patients had late seizures, which were multiple in 4 (4.8%). Late seizures were more frequent in patients with early symptomatic seizures and with haemorrhage on admission CT/MR. Neither early symptomatic seizures nor late seizures were related to functional prognosis at the last follow-up (median = 1 year). There is a moderate risk of seizure recurrence early in the course and during the first year after CVDST. Seizures can be a cause of acute death, but might not have an independent influence on functional outcome. Pharmacological prevention of seizures after CVDST should probably be limited to patients with early symptomatic seizures and cerebral lesions on admission CT/MR.
The purpose of this study was to analyze the long-term mortality, functional recovery and long-term complications of cerebral vein and dural sinus thrombosis (CVDST) admitted to Portuguese hospitals. A follow-up of symptomatic CVDST admitted to Portuguese hospitals since 1980 was performed. Fifty-one patients (retrospective cases) were re-evaluated during 1996; 91 consecutively admitted patients from 6/1995 to 6/1998 were followed up to 1999. In 1996, 4 (8%) of the retrospective cases had died (3 patients died in the acute phase), 4 (8%) could not be reached, 33 (64%) had recovered completely (Rankin 0 or 1) and 3 (6%) were dependent. The prospective cases had a mean follow-up of 1 year: 6 (7%) patients died in the acute phase, one (1%) died during follow-up, 75 (82%) recovered completely, and only 1 (1%) was dependent. For the prospective cases, worsening after admission (OR = 18.2; 95% CI = 2.9-112.4) and encephalopathy as the presenting syndrome (OR = 7.1; 95% CI = 1.2-40.9) predicted death or dependency, while absence of aphasia (OR 6.7, 95% CI = 1.6-33) and no worsening after admission (OR = 5.9; 95% CI = 1.6-20) predicted total recovery. During follow-up of the prospective cases, 4 (5%) patients had thrombotic events, 8 (10%) patients experienced seizures, 9 (11%) complained of severe headaches and 1 patient suffered severe visual loss. The long-term functional prognosis of patients with CVDST was fairly good with complete recovery in the majority of cases. However, these patients had a moderate risk of further thrombotic events and seizures.
We report a biopsy-proven case of progressive multifocal leukoencephalopathy (PML) in a pregnant woman without obvious underlying immune disorder. MRI showed lesion enhancement and deep gray matter involvement, which are uncommon imaging patterns in PML. The clinical course in this case is also rather atypical, as the patient is alive 16 months after disease onset. The combination of these unusual characteristics in PML is unknown and indicates that the criteria for this disease may need to be redefined.
BACKGROUND AND PURPOSE: The first medical contact of an acute stroke victim is often a nonneurologist. Validation of stroke diagnosis made by these medical doctors is poorly known. The present study seeks to validate the stroke diagnoses made by general practitioners (GPs) and hospital emergency service physicians (ESPs). METHODS: Validation through direct interview and examination by a neurologist was performed for diagnoses of stroke made by GPs in patients under their care and doctors working at the emergency departments of 3 hospitals. RESULTS: Validation of the GP diagnosis was confirmed in 44 cases (85%); 3 patients (6%) had transient ischemic attacks and 5 (9%) suffered from noncerebrovascular disorders. Validation of the ESP diagnosis was confirmed in 169 patients (91%); 16 (9%) had a noncerebrovascular diagnosis. Overall, the most frequent conditions misdiagnosed as stroke were neurological in nature (cerebral tumor, 3; subdural hematoma, 1; seizure, 1; benign paroxysmal postural vertigo, 1; peripheral facial palsy, 2; psychiatric condition, 6; and other medical disorders, 7). CONCLUSIONS: In the majority of cases, nonneurologists (either GPs or ESPs) can make a correct diagnosis of acute stroke. Treatment of acute stroke with drugs that do not cause serious side effects can be started before evaluation by a neurologist and CT scan.
BACKGROUND: Elston and Russell discovered a difference in the biological potency of the English formulation of botulinum toxin type A or BTX-A (Dysport) and the American formulation (Botox). Potency of both is expressed in LD50 mouse units, but because of assay differences, these units are not equivalent. Since the first warning by Quinn and Hallet on the clinical importance of this issue, it has been impossible to reach a consensus on the conversion factor for the potency of these formulations. OBJECTIVE: To test the hypothesis that the conversion factor for the clinical potency of Dysport to Botox is approximately 4:1. DYSBOT is an acronym that results from adding "DYS" from Dysport with "BOT" from Botox. PATIENTS AND METHODS DESIGN: A single-blind, randomized, parallel comparison. A total of 91 patients with blepharospasm or hemifacial spasm were randomized to treatment with Dysport or Botox using a fixed potency ratio of 4:1. Clinical evaluations: The patients were evaluated at baseline (day of the treatment). 1 month after treatment, and whenever the effect was judged to be fading. Objective and functional rating scales were used as quantitative measures of the change in clinical status. Adverse reactions were collected using a systematic questionnaire. RESULTS: Using this ratio between products, both Dysport and Botox groups produced similar clinical efficacy and tolerability. For patients showing a positive response without the need of a booster, the duration of effect was 13.3 +/- 5.9 weeks for the Dysport group and 11.2 +/- 5.8 weeks for the Botox group. Of 48 patients, 11 (23%) needed booster treatment in the Dysport group compared with five (12%) of 43 in Botox group. Adverse events were noted in 24 (50%) of 48 patients in the Dysport group and 20 (47%) of 43 of the Botox-treated group. CONCLUSIONS: Using a 4:1 conversion ratio for Dysport and Botox, similar results were obtained for the two treatments in an appropriately powered study, suggesting that this conversion factor is a good estimate of their comparative clinical potencies.
A 6 year old Portuguese boy with dilated cardiomyopathy had abundant ragged red fibres in muscle (20% of total) and severe lactic acidosis. Molecular genetic analysis showed the A to G transition in the mitochondrial transfer RNALeu(UUR) gene at nt 3243 ("MELAS mutation"), which accounted for 88% and 68% of the total mtDNA in his muscle and blood, respectively. Molecular studies in blood from 16 maternal relatives identified lower percentages of the mutation only in the oligo-symptomatic mother and brother. This case reinforces the notion that cardiomyopathy can be the presenting and predominant clinical expression of the A3243G mutation.
The relationships between migraine and A-V Malformations is a subject of controversy and the arguments are mainly based on case reports and retrospective data. To clarify this subject a structured inquiry and classification of headaches in large samples of patients with intracranial vascular malformations (IVM) is essential. The authors studied the prevalence of headaches in 51 patients with IVM admitted to our Department, between 1984 and 1992. The methods used were a review of medical records followed by a self-administered headache questionnaire and clinical interview using the IHS criteria for the diagnostic classification of headaches. The relative frequency of the different types of headaches was calculated and compared with the general population data. A correlative study of the headache characteristics with the type and location of the IVM was made. A high prevalence (47%) of migraine type headaches and a strong positive correlation (88.8%) between the site of AVM and side of the pain was found. This is highly suggestive but not conclusive of a pathophysiologic relationship between these entities. The conclusion drawn is that a prospective study of headaches by questionnaire or semi-structured clinical interview in patients with IVM is essential to discover the effective prevalence and characteristics of headaches associated with IVM and their relationships.