Cerebral venous sinus thrombosis in childhood: clinical aspects and neurological and cognitive long-term outcome in three cases.

We report clinical findings, risk factors and neurological and cognitive long-term outcome in three Italian children aged 7, 8 and 5, respectively, who experienced cerebral venous sinus thrombosis (CVST). All children presented with headache, associated to nausea, vomiting and papilloedema. None suffered from epileptic seizures. In two of them a paresis of the sixth cranial nerve with diplopia was found. Diagnosis was confirmed by magnetic resonance imaging angiography (angio MRI) in all cases. In all patients plasma levels of protein C, protein S, antithrombin III (AT III), antiphospholipid antibodies (ApA) and homocysteine were detected. Furthermore, factor V Leiden mutation, prothrombin mutation G20210A and MTHFR mutation were searched for. A Protein C reduction was detected in all patients at onset; this finding, however, was not confirmed at follow-up in all of them. At one-year follow-up, neurological examination was normal in all children and neuropsychological assessment, aimed at excluding linguistic and non-linguistic cognitive deficits, revealed normal performances in two of them. In the third child, cognitive assessment confirmed a previously diagnosed developmental dyslexia.

Small fibers peroneal mononeuropathy in a patient with Sjögren's syndrome.

Sjögren's syndrome (SS) is an autoimmune epithelitis characterized by lymphocytic infiltration of exocrine glands and epithelia in multiple sites. One third of the patients present with peripheral nervous system involvement. We describe the case of a woman aged 62 affected by a peroneal nerve mononeuropathy with painful disturbances secondary to a prevalent involvement of small fibers as demonstrated by electrophysiological investigations and skin biopsy. Asymmetric peripheral nerve involvement is not uncommon in SS, though, to our knowledge, it has never been reported of a mononeuropathy involving primarily small fibers.

Creutzfeldt-Jakob disease with a novel extra-repeat insertional mutation in the PRNP gene.

The authors investigated two unrelated patients with Creutzfeldt-Jakob disease (CJD) with clinical features of sporadic CJD (sCJD) carrying one extra octapeptide repeat in the prion protein (PrP) gene (PRNP). A synaptic type PrP distribution throughout the cerebral gray matter and plaque-like PrP deposits in the subcortical gray structures were detected immunocytochemically. The different patterns of PrP deposition were associated with distinct types of protease-resistant PrP, similar to type 1 and type 2 of sCJD. The features suggest that this insertion is a pathogenic mutation.

Neurological and cognitive long-term outcome in patients with cerebral venous sinus thrombosis.

OBJECTIVES: The main aim of the present study was to assess long-term neurological and cognitive outcome in patients with cerebral venous sinus thrombosis (CVST). METHODS: We re-investigated by means of a face to face interview all patients with a confirmed diagnosis of CVST, collected at our Department over the years 1990-2000. During the interview the presence of headache, epileptic seizures, visual deficits and a new episode following the first occurrence of CVST were checked. Moreover all patients underwent a neurological examination, a functional evaluation, a cognitive assessment to rule out aphasia, apraxia and working memory deficits. Depression of mood was also investigated. RESULTS: On the whole 34 patients entered the study: 10 patients referred episodic headache following the disease. In three cases epileptic seizures were present. A new event occurred in only one patient. Four patients showed pyramidal signs, in two cases visual deficits were present. All patients had no functional disability. We found a mild non-fluent aphasia in three patients, working memory deficits in six patients and depression of mood in six cases. CONCLUSION: The present study demonstrates a good neurological and cognitive long-term outcome in patients with CVST.

Frontal intermittent rhythmic delta activity (FIRDA) in patients with dementia with Lewy bodies: a diagnostic tool?

The accuracy of the clinical diagnosis of dementia with Lewy bodies (DLB) remains poor, especially in early phases of the disease, in spite of applying current consensus diagnostic criteria. The need for supportive diagnostic tools is therefore warranted. In this study EEG recordings showed a main pattern of bilateral frontal intermittent rhythmic delta activity (FIRDA) in 7 of 10 patients, aged 58-83 years, 8 of whom were diagnosed as affected by "probable" and 2 by "possible" DLB. Conversely, the same EEG abnormality was found only in 2 of 9 age-matched patients, 8 of whom had "probable" and 1 "possible" Alzheimer's disease, according to NINCDS-ADRDA criteria, taken as controls. The degree of cognitive impairment was comparable among the two groups of patients. If these findings will be confirmed in a larger series, FIRDA, even though an aspecific EEG pattern, could be of value in improving the diagnostic accuracy of DLB.

Masseteric repetitive nerve stimulation in the diagnosis of myasthenia gravis.

OBJECTIVE: (1) to develop a method for masseteric repetitive nerve stimulation (RNS) and to obtain normative data for amplitude and area decrement of the muscle (M) response. (2) To investigate myasthenia gravis (MG) patients with masseteric RNS. Masticatory muscles are frequently affected in MG, but no RNS test is available to investigate this district. METHODS: Fifteen healthy subjects and 17 MG patients were examined. The masseteric nerve was stimulated by a monopolar needle (cathode), inserted between the mandibular incisure and the zygomatic arch, and a surface electrode (anode), on the contralateral cheek. Masseteric M response was recorded using surface electrodes on the muscle belly and below the mandibular angle. Stimuli were delivered at 3 Hz in trains of 9, at rest and after isometric effort. RESULTS: Normal subjects: mean amplitude decrement was 0.3+/-1.2% at rest, and 1.9+/-1.3% after isometric effort. PATIENTS: 15 patients (88%) were positive on masseteric RNS; in 3 of these it was the only positive RNS test. The extent of decrement observed in masseter muscle was significantly greater than in trapezius muscle. CONCLUSIONS: Masseteric RNS is a simple and well-tolerated procedure; it offers a new possibility in testing the cranial muscles in disorders of neuromuscular transmission.

Loco-regional thrombolysis in the treatment of cerebral venous and sinus thrombosis: report of two cases.

Although intravenous (i.v.) heparin is widely used as the first line treatment for cerebral venous and sinus thrombosis (CVST), the most appropriate therapy for this disease is still controversial. We report 2 cases of CVST who were successfully treated by means of loco-regional thrombolysis with urokinase. In the first case we chose this treatment instead of i.v. heparin because clinical conditions of the patient appeared critical for life on hospital admission; in the second case loco-regional thrombolysis was performed because a full-dose heparin treatment over 8 days failed to improve the clinical picture of the patient. In the literature, there are no established criteria for the use of loco-regional thrombolysis in CVST. On the basis of our own experience and few previous reports on the matter, we suggest that loco-regional thrombolysis should be considered an appropriate treatment for CVST when patients are at life risk, when an involvement of deep cerebral veins is present or when, after full heparinization, patients are doing poorly clinically.

Trigemino-facial reflex inhibitory responses in some lower facial muscles.

The effects of electrical trigeminal stimulation on activated facial muscles were studied in 20 normal subjects in order to evaluate whether excitatory or inhibitory responses are present and to investigate whether the reflex organization is similar in all the facial muscles. No inhibition was observed in frontalis, orbicularis oculi, orbicularis oris, and mentalis muscles. By contrast, a clear suppression of electromyographic (EMG) activity (late silent period or SP2) was present in the levator labii superioris, depressor anguli oris, and depressor labii inferioris muscles, with a mean latency ranging from 41.8 to 50.2 ms, and a mean duration ranging from 27.5 to 40.9 ms. An early suppression of EMG activity (early silent period or SP1) was observed, with a latency of 16 to 20 ms and a duration of 10 ms, mainly in inferior perioral muscles. Our findings show a selective trigeminal inhibitory influence upon some specific lower facial muscles.

Low-oestrogen oral contraceptives as a major risk factor for cerebral venous and sinus thrombosis: evidence from a clinical series.

Cerebral venous and sinus thrombosis (CVST) is still considered a severe clinical problem that is difficult to diagnose and manage and is linked to a poor prognosis. Nonetheless, conventional cerebral angiography and magnetic resonance imaging (MRI), or more recently, MR angiography allow a more rapid and precise diagnosis, and prognosis has improved with the use of anticoagulant treatment. We report 23 cases of CVST consecutively admitted to the Institute of Neurology of the University of Parma during the period 1990-1997. In all cases diagnosis was confirmed by means of MRI or conventional angiography of brain vessels. Among the patients, 22 were female and 1 was male. In all patients, plasma levels of protein C, protein S, antithrombin III (ATIII) and antiphospholipid antibodies (APA) were evaluated. In 15 of 23 patients, the presence of factor V Leiden mutation was also determined, and found positive in 3 patients (20%). Of the 22 female patients, 15 (68%) were on low-oestrogen (containing less than 50 microg oestrogen) oral contraceptive (OC) treatment. This percentage of OC use by patients with CVST is much higher than that of the rest of the female Italian population. OC use was associated with the presence of factor V Leiden mutation in two cases, with a deficiency of protein C in 1 case and a deficiency of protein S in another.Whether low-oestrogen Ocs may induce cerebral thromboembolic events is an open matter. According to our data, it may be argued that Ocs, even if at low oestrogen content, represent a major risk factor for CVST. The use of Ocs, as is the case for systemic venous thromboembolic events, may further increase the risk of CVST in women carrying the factor V Leiden mutation or other inherited hyperthrombotic conditions.

Triphasic waves associated with acute naproxen overdose: a case report.

Triphasic waves (TWs) can be recorded on EEG in the course of several metabolic disorders, mainly hepatic encephalopathy. A case of acute encephalopathy due to naproxen intoxication is reported, in the course of which diffuse, bilateral and symmetrical TWs were recorded. Biochemical mechanisms that might determine both a complex encephalopathy and TWs are discussed.

The masseteric inhibitory reflex in the diagnosis of multiple sclerosis.

In order to evaluate the reliability of the masseteric inhibitory reflex (MIR) as a screening method in the diagnosis of multiple sclerosis (MS), a series of 41 consecutive patients affected by clinically defined, long-duration forms (mean duration 10.9 years) of the disease was examined. In all cases magnetic resonance imaging and CSF isoelectrofocusing confirmed the diagnosis. Sensitivity of MIR, Blink Reflex and BAEPs were compared. Statistical analysis of data suggested the following considerations: 1) a significant concordance was found between MIR and the other neurophysiological tests performed (MIR vs. BAEPs in 78.4% of cases, p < 0.001; MIR vs. blink reflex in 68.3%, p < 0.02). 2) The S1 early component of MIR is a more reliable indicator than S2 late component. 3) In detecting brainstem lesions the sensitivity of MIR equaled that of the other neurophysiological tests. 4) Poor localizing concordance between neurophysiological tests and neuroimaging was found in our series. A possible utilization of MIR, as a part of a multimodal neurophysiological approach, even in patients affected by possible or probable MS is suggested.

Risk of acute cerebrovascular events related to low oestrogen oral contraceptive treatment.

To establish if an association exists between use of oral contraceptives (OC) and the occurrence of cerebral arterial thromboembolism, cerebral venous thrombosis and retinal vein/artery thrombosis, we identified all women aged 15-44 years resident in the province of Parma, Italy, who were hospitalized because of a documented cerebral or retinal thromboembolic event during the period 1989-1993. The numbers of users and nonusers of OC were estimated from drug sale data and demographic statistics for the province. There were 21 cases of cerebral arterial thromboembolism during the study period: 10 in OC users and 11 in nonusers, for an estimated incidence rate of 1.70 and 0.35 per 10,000 woman-years OC of use and nonuse, respectively (RR=4.8, 95% CI = 1.8-9.0). Eight cases of cerebral venous thrombosis were observed: 6 in OC users and 2 in nonusers (both in puerperium), for an incidence rate of 1.00 and 0.06 per 10,000 woman-years, respectively (RR=16.7, 95% CI = 3.3-81.4). Finally, 13 cases of retinal vein/artery thrombosis were found: 1 in OC users and 12 in nonusers, for an incidence rate of 0.17 and 0.37 per 10,000 woman-years, respectively (RR=0.46, 95% CI = 0.06-3.7). In our population study the use of low oestrogen OC was associated with an increased risk of cerebral venous thrombosis and ischemic stroke, but not of retinal vein/artery thrombosis.

Diffuse thalamic degeneration in fatal familial insomnia. A morphometric study.

A morphometric investigation disclosed most thalamic nuclei severely degenerated in two patients with fatal familial insomnia. Associative and motor nuclei lost 90% neurons, and limbic-paralimbic, intralaminar and reticular nuclei lost 60%. These findings point to the disorganization of most thalamic circuits as a condition necessary for the sleep-wake rhythm being affected.

Randomised, double-blind, placebo-controlled study of pivagabine in neurasthenia.

One hundred and eighteen patients with neurasthenia, as defined by ICD 10 (International Classification of Diseases), participated in a randomised, double-blind, placebo-controlled trial of pivagabine (4-[(2,2-dimethyl-1-oxopropyl)amino]butanoic acid, CAS 69542-93-4, Tonerg). Pivagabine 1800 mg/d was administered orally for four weeks. At the end of the trial, active medication was significantly superior to placebo on the Clinical Global Impression (CGI) improvement of illness scale. In addition, pivagabine treatment reduced the physical and mental fatigability of patients, and increased their sense of well-being.

Spindle coma and alternating pattern in the course of measles encephalitis.

Acute disseminated encephalomyelitis (ADEM) is a well known complication of measles infection. Electroencephalographic abnormalities may occur frequently, in the form of moderate to severe diffuse high voltage theta-delta activity. We report a case of measles encephalitis with rapid benign outcome, that showed peculiar EEG features both of a "spindle coma" pattern and of an "alternating pattern." Possible physiological explanations of the EEG findings are discussed.

Precocious loss of physiological sleep in a case of Creutzfeldt Jakob disease: a serial polygraphic study.

Creutzfeldt-Jakob disease (CJD) is a prion-related subacute encephalopathy producing widespread neuronal degeneration and spongiform pathological changes, especially in the neocortex. Progressive dementia, motor signs and electroencephalographic (EEG) alterations characterize the full stage of the disease. A series of eight 24-hour polygraphic recordings were carried out in the last 3 months of life of a 68-year-old female patient affected by CJD that was confirmed neuropathologically. Genetic classification demonstrated this patient to have a sporadic form of the disease. The polygraphic recordings demonstrated three types of EEG findings, as follows: 1) sustained pseudoperiodic discharges (SPD), characterized by long-lasting diffuse sequences of slow sharp waves or di- or triphasic slow waves recurring at 0.5- to 1.5-second intervals; 2) discontinuous pseudoperiodic discharges (DPD), consisting of runs of pseudoperiodic discharges (PD)(phase A) cyclically replaced at about 1-minute intervals with semi-rhythmic theta-delta activities (phase B); 3) non-rapid eye movement (NREM) sleep-like pattern, with dominant 0.5- to 4-Hz activities, less rhythmic than the EEG of phase B. Only these three EEG patterns occurred spontaneously during the repeated polygraphic sessions. The NREM sleep-like pattern was found only in the first recording, whereas the following polygraphic sessions were occupied exclusively by SPD or by a DPD pattern. SPD was associated with either a relatively high level of vigilance (along the first three recordings) or a state of alert-appearing silent immobility (following the fourth recording). During DPD, the patient was unable to accomplish any voluntary movement and fluctuated between levels of greater arousal (phase A) and lesser arousal (phase B). Just as in stage 2 coma, the fluctuations between phases A and B of DPD were synchronous with phasic modifications of muscle activity and neurovegetative functions. In particular, reinforcement of muscle tone and myoclonic spasms coincided with phase A, whereas heart rate deceleration and respiratory pauses or decrease in flow were synchronous with phase B. As EEG evolved toward the disappearance of DPD and finally to flatness, the phase-locked coordination among arousal, somatic and vegetative activities was progressively impaired and was replaced with an uncontrolled exaggeration of cardiorespiratory activity. The genetic, neuropathological and polysomnographic differences between CJD and another prion disease, fatal familial insomnia, are discussed.