ECG monitoring of post-stroke occurring arrhythmias: an observational study using 7-day Holter ECG.

Post-stroke arrhythmias represent a risk factor for complications and worse prognosis after cerebrovascular events. The aims of the study were to detect the rate of atrial fibrillation (AF) and other cardiac arrhythmias after acute ischemic stroke, by using a 7-day Holter ECG which has proved to be superior to the standard 24-h recording, and to evaluate the possible association between brain lesions and arrhythmias. One hundred and twenty patients with cryptogenic ischemic stroke underwent clinical and neuroimaging assessment and were monitored with a 7-day Holter ECG. Analysis of the rhythm recorded over 7 days was compared to analysis limited at the first 24 h of monitoring. 7-day Holter ECG detected AF in 4% of patients, supraventricular extrasystole (SVEB) in 94%, ventricular extrasystole (VEB) in 88%, short supraventricular runs (SVRs) in 54%, supraventricular tachycardia in 20%, and bradycardia in 6%. Compared to the first 24 h of monitoring, 7-Holter ECG showed a significant higher detection for all arrhythmias (AF p = 0.02; bradycardia p = 0.03; tachycardia p = 0.0001; SVEB p = 0.0002; VEB p = 0.0001; SVRs p = 0.0001). Patients with SVRs and bradycardia were older (p = 0.0001; p = 0.035) and had higher CHA2DS2VASc scores (p = 0.004; p = 0.026) respectively, in the comparison with patients without these two arrhythmias. An association was found between SVEB and parietal (p = 0.013) and temporal (p = 0.013) lobe lesions, whereas VEB correlated with insular involvement (p = 0.002). 7-day Holter ECG monitoring proved to be superior as compared to 24-h recording for the detection of all arrhythmias, some of which (SVEB and VEB) were associated with specific brain areas involvement. Therefore, 7-day Holter ECG should be required as an effective first-line approach to improve both diagnosis and therapeutic management after stroke.

Recurrent and fatal akinetic crisis in genetic-mitochondrial parkinsonisms.

BACKGROUND AND PURPOSE: Akinetic crisis (AC) is the most severe and possibly lethal complication of parkinsonism. It occurs with an incidence of 3‰ Parkinson's disease patients per year, but it is not known whether genetically determined parkinsonism is more or less susceptible to this complication. METHODS: In a cohort of 756 parkinsonian patients the incidence and outcome of AC was prospectively assessed. A total of 142 of the parkinsonian patients were tested for genetic mutations because of familial parkinsonism, and 20 patients resulted positive: in four the mutation definitely involved mitochondrial functions (POLG1, PINK1), two presented with LRRK2 mutation, nine presented with GBA mutation and five presented with Park 4 different mutations. RESULTS: Akinetic crisis occurred in 30 patients for an incidence of 2.8‰ persons/year and was lethal in seven (23%), not dissimilarly from known incidences of this complication. Yet six of 30 patients were carriers of genetic mutations, one GBA, one LRRK2, one POLG1 and three PINK1. In POLG1 and PINK1 carriers, the syndrome was recurrent and was fatal in three. Incidence of AC was 3.0‰ in familiar parkinsonism, 21.2‰ in genetic parkinsonisms. CONCLUSIONS: Our preliminary findings suggest that the incidence of AC is remarkably increased in carriers of these genetic mutations.

Long half-life and prolonged-release dopamine receptor agonists: a review of ropinirole prolonged-release studies.

Our review summarizes the five main studies conducted to evaluate the efficacy and pharmacokinetics of ropinirole prolonged release (PR) in Parkinson's disease (PD). The PR formulation was developed with Geomatrix coating technology in order to obtain constant pharmacokinetics throughout 24 hours. The areas under the curve were not significantly different from those observed with similar doses of ropinirole immediate-release (IR) formulation, administered 3 times a day, but concentration fluctuations were less for ropinirole PR (2-fold vs 5-fold). The efficacy study of the PR versus IR formulations showed non-inferiority of the PR formulation, similar tolerability and feasibility of overnight switches, and indicated that the optimal doses of ropinirole in patients with de novo PD is in the range of 8-12 mg/day. The efficacy study in PD patients with motor fluctuations treated with L-dopa showed that adding ropinirole PR significantly reduced "off" time and increased "on" time in comparison with placebo. The study with ropinirole as an add-on to L-dopa showed a reduced incidence of dyskinesias.

Efficacy of a soft hand brace and a wrist splint for carpal tunnel syndrome: a randomized controlled study.

OBJECTIVE: To examine, in a randomized, controlled, single blinded trial, the efficacy of a soft hand brace and a wrist splint for carpal tunnel syndrome (CTS). METHODS: We randomized 120 patients with CTS into a group wearing the soft hand brace MANU and into another group wearing the wrist splint CAMP TIELLE at night for 3 months. We re-evaluated the patients after 3 (T1) and 9 months (T2). The primary efficacy measures were changes in scores of Boston Carpal Tunnel Questionnaire (BCTQ) and in Visual Analogical Scale (VAS) for pain and paresthesias. RESULTS: At T1, both groups showed a significant reduction in symptomatic and functional BCTQ (T0-T1 differences: MANU BCTQ sympt: 0.88 (0.68-1.08), funct: 0.45 (0.19-0.72); TIELLE BCTQ sympt: 0.78 (0.55-1.01), funct: 0.41 (0.22-0.59). At T2, a less evident benefit on symptoms persisted in both groups, except for pain VAS score that was significantly reduced only in the CAMP TIELLE group. No significant functional benefits persisted in either group. There were no differences in BCTQ and VAS scores between the two groups at T1 and T2 compared with that at baseline. CONCLUSIONS: A 3-month treatment with either the hand brace or the wrist splint induces a symptomatic and functional benefit in patients with CTS.

Segmental conduction abnormalities and myelin thickenings in Val102/fs null mutation of MPZ gene.

The authors report in patients with Val102/fs null mutation a possibly age dependent variability of clinical and electrophysiologic phenotype, segmental conduction abnormalities mainly in ulnar nerves at the elbow, and excessive myelin foldings and thickenings. The authors hypothesize that myelin thickenings at the paranodal region, in concurrence with compression at usual entrapment sites or minor repetitive trauma, may induce segmental conduction abnormalities.

Inter-nerves and intra-nerve conduction heterogeneity in CMTX with Arg(15)Gln mutation.

OBJECTIVE: In X-linked Charcot-Marie-Tooth disease (CMTX), electrophysiological and histopathological studies have suggested either a demyelinating or an axonal polyneuropathy. We report a CMTX family with a striking heterogeneity of nerve conductions between and within nerves. METHODS: Two men and one woman have been studied by conduction velocities, sural nerve biopsy with morphometry (one man) and DNA analysis. RESULTS: In both men motor conduction velocities were slowed in the demyelinating range, conduction velocity differences among nerves in the same subject varied from 13 to 24 m/s, and distal median compound muscle action potential (CMAP) amplitudes were 3-5 times reduced compared to ulnar CMAPs. Abnormal area reduction or excessive temporal dispersion of proximal CMAP was present in at least two nerves in all patients. Sural nerve biopsy showed reduction of large myelinated fibres, cluster formations, occasional onion bulbs. Teased fibres study revealed short internodes for fibre diameter, enlarged Ranvier nodes but no evidence of segmental demyelination and remyelination. DNA analysis showed an Arg(15)Gln mutation in connexin32 gene in all patients. CONCLUSIONS: In this family conduction slowing and segmental conduction abnormalities, in absence of morphological evidence of de-remyelination, may be related to short internodes, widened Ranvier nodes and the specific effect of the mutation. The occurrence in some CMTX patients of a non uniform involvement between and within nerves, as in acquired demyelinating neuropathies, should be kept in mind to avoid misdiagnoses.

Dysmyelinating sensory-motor neuropathy in merosin-deficient congenital muscular dystrophy.

A 20-year-old man with mild myopathy, external ophthalmoparesis, epilepsy, and diffuse white matter hyperintensity in the brain on magnetic resonance imaging had partial merosin deficiency in muscle and absent merosin in the endoneurium. Motor and sensory nerve conduction velocities were slow. Nerve biopsy showed reduction of large myelinated fibers, short internodes, enlarged nodes, excessive variability of myelin thickness, tomacula, and uncompacted myelin, but no evidence of segmental demyelination, naked axons, or onion bulbs. Thus, in congenital muscular dystrophy, merosin expression may be dissociated in different tissues, and the neuropathy is sensory-motor and due to abnormal myelinogenesis.

Facioscapulohumeral muscular dystrophy presenting isolated monomelic lower limb atrophy. Report of two patients with and without 4q35 rearrangement.

Facioscapulohumeral muscular dystrophy has a distinctive regional distribution but variable clinical expression and may be markedly asymmetrical. We report two patients presenting weakness and wasting confined to a single lower limb. Creatine kinase was slightly increased, electromyogram and muscle biopsy were myopathic. Muscle computed tomography showed normal shoulder, mid-arm, pelvic and mid-thigh scans but involvement of calf muscles. In both cases, weakness of facial and periscapular muscles was found in other family members unaware of the disease. Molecular analysis showed 4q35 deletion in one family. These cases broaden the presentation of facioscapulohumeral muscular dystrophy to include isolated monomelic atrophy of lower limb with calf muscle involvement.

Autosomal dominant distal spinal muscular atrophy: an Italian family not linked to 12q24 and 7p14.

Distal spinal muscular atrophy is genetically heterogeneous, as sporadic cases and both autosomal dominant and recessive inheritance have been described. An autosomal dominant distal spinal muscular atrophy with upper limb predominance has been mapped to chromosome 7p, and more recently, an autosomal dominant distal spinal muscular atrophy with lower limb predominance has been linked to chromosome 12q24. We describe a four generation Italian family with autosomal dominant distal spinal muscular atrophy starting between 8 and 30 years with weakness and atrophy of distal leg muscles. The older patients also presented sensorineural deafness. We performed genetic linkage analysis with microsatellite markers D12S366, D12S349, D12S86, D12S321, D12S1612, D12S1349, D12S342, PLA2A on chromosome 12q24 and D7S516, D7S2496, D7S632, D7S2252 on chromosome 7p14. No support for linkage to chromosome 12q24 and 7p14 was found in our family, confirming a genetic heterogeneity within autosomal dominant distal spinal muscular atrophy.

Anti-GD1a antibodies from an acute motor axonal neuropathy patient selectively bind to motor nerve fiber nodes of Ranvier.

Acute motor axonal neuropathy (AMAN) is associated with high titer anti-GD1a antibodies. We have found that very high titer IgG anti-GD1a antibodies (Ab) from one AMAN patient selectively bind to motor, but not sensory, nerve nodes of Ranvier. Binding is abolished by preadsorption with GD1a. Sera negative for Ab do not immunostain motor and sensory nerve roots. We have also found that botulinum toxin A (BTA), which binds to GD1a, stains both motor and sensory nerve nodes of Ranvier. Our results strongly support the pathogenetic role of anti-GD1a antibodies in AMAN. Why BTA also binds to sensory fibers still remains to be elucidated, although the different size of BTA and its specificity to other gangliosides present in sensory axons might represent important factors.

Minimal and asymptomatic chronic inflammatory demyelinating polyneuropathy.

OBJECTIVES: Show the chronic inflammatory demyelinating polyneuropathy (CIDP) is not only clinically heterogeneous but extremely variable in severity. METHODS: Three patients were referred for mild distal paresthesiae lasting more than 6 months and one for inguinal and thigh pain later ascribed to coxarthrosis. Strength was normal in all patients and tactile sensation reduced distally only in one. Tendon jerks were absent, except the knee jerks in one patient, reduced in lower limbs in two and normal in one. RESULTS: Electrophysiology showed a demyelinating neuropathy without motor conduction block. CSF protein content was increased in all patients. Nerve biopsies showed de-remyelination with varying degrees of axonal loss. Genetic studies excluded a demyelinating neuropathy associated with duplication or deletion of the 17p.11.2 segment. CONCLUSIONS: CIDP patients with pure sensory clinical presentation have been described but are generally more severely impaired. However, because of the mildness of symptoms and the unequivocal electrophysiological involvement of motor fibers, we think that in these cases the term minimal CIDP is more appropriate than sensory CIDP. These cases represent the most benign end of the CIDP spectrum. In our series minimal or even asymptomatic CIDP encompasses 8% of cases.

Chronic inflammatory demyelinating polyneuropathy in diabetics: motor conductions are important in the differential diagnosis with diabetic polyneuropathy.

OBJECTIVE: It is important to recognize CIDP occurring in diabetics because, unlike diabetic polyneuropathy, it is treatable. The aim of this study was to find out whether there are clues which help to differentiate CIDP in diabetics from diabetic polyneuropathy. METHODS: We compared the electrophysiological and pathological findings of 7 diabetics, who developed a predominantly motor polyneuropathy with the features of CIDP, with a group of diabetics referred for symptomatic polyneuropathy. RESULTS: Of the 7 diabetics we believe developed CIDP, 6 met at least 3 and one patient two of the 4 electrophysiological criteria of demyelination. Of the 100 patients referred for diabetic polyneuropathy, only 4 fulfilled two criteria and none 3. Nerve biopsy findings were not helpful in differential diagnosis, as segmental demyelination and remyelination, onion bulbs and inflammatory infiltrates, which are the histologic features of CIDP, were also present in diabetic polyneuropathy. CONCLUSIONS: CIDP can be diagnosed in a diabetic patient when motor symptoms are predominant, are more severe than expected in diabetic polyneuropathy and 3 of the 4 electrophysiological criteria for demyelination are fulfilled. When only two criteria are met, we believe that a trial with one of the established treatments for CIDP may be helpful in confirming the diagnosis.

Effect of rhTNF-alpha injection into rat sciatic nerve.

To assess whether TNF-alpha causes inflammatory demyelination or axonal degeneration, we injected into rat sciatic nerve saline, 100 U and 1000 U of rhTNF-alpha and studied the electrophysiological and pathological effects. At day 1 electrophysiology showed a slight reduction of proximal compound muscle action potential amplitude and pathology showed edema, inflammatory infiltration of vessel walls and endoneurium only in nerves injected with 1000 U of rhTNF-alpha. At day 5, there was no demyelination and a percentage of degenerated fibers similar in the three groups. To study the blood-nerve barrier, fluorescein isothiocyanate-labelled albumin was given intravenously after intraneural injection. The nerves injected with 1000 U rhTNF-alpha showed a leakage of the tracer in the endoneurium. TNF-alpha does not appear, at the doses used, to have myelinotoxic or axonopathic properties. The electrophysiological effect at day 1 may be due to mechanical compression of nerve fibers as a result of the blood-nerve barrier damage with consequent endoneurial edema.

Low back pain due to hypertrophic roots as presenting symptom of CIDP.

Attention has recently been drawn to chronic inflammatory demyelinating polyneuropathy (CIDP) with symptomatic nerve root hypertrophy. A 31-year-old woman had fluctuating and worsening low back pain. Absent tendon jerks and a slight weakness of the hand interossei muscles suggested a diffuse neuropathy. The electrophysiological and histological findings were diagnostic for CIDP. Lumbar spine MRI showed marked nerve root enlargement with gadolinium enhancement. This case widens the range of the clinical presentations of CIDP. Further studies are warranted to ascertain whether cauda equina gadolinium enhancement may be a useful tool in the diagnosis of CIDP and a marker of disease activity for monitoring response to therapy.