To determine whether somatosensory temporal discrimination will reliably detect subclinical sensory impairment in patients with various forms of primary focal dystonia.
The somatosensory temporal discrimination threshold (STDT) was tested in 82 outpatients affected by cranial, cervical, laryngeal and hand dystonia. Results were compared with those for 61 healthy subjects and 26 patients with hemifacial spasm, a non-dystonic disorder. STDT was tested by delivering paired stimuli starting with an interstimulus interval of 0 ms followed by a progressively increasing interstimulus interval.
STDT was abnormal in all the different forms of primary focal dystonias in all three body regions (eye, hand and neck), regardless of the distribution and severity of motor symptoms. Receiver operating characteristic curve analysis calculated in the three body regions yielded high diagnostic sensitivity and specificity for STDT abnormalities.
These results provide definitive evidence that STDT abnormalities are a generalised feature of patients with primary focal dystonias and are a valid tool for screening subclinical sensory abnormalities.
Swallowing dysfunction is common and disabling after acute stroke; however, the mechanism of dysphagia or recovery of swallowing from dysphagia remains uncertain. The purpose of this study was to explore cerebral activation of swallowing in dysphagia using functional MRI (fMRI) to compare the functional anatomy of swallowing in unilateral hemispheric stroke patients and healthy adults.
In total, five left hemispheric stroke patients with dysphagia, five right hemispheric stroke patients with dysphagia and 10 healthy controls were examined with event related fMRI while laryngeal swallow related movements were recorded. Data were processed using the general linear model.
A multifocal cerebral representation of swallowing was identified predominantly in the left hemisphere, in a bilateral and asymmetrical manner. Cerebral activation during swallowing tasks was localised to the precentral, postcentral and anterior cingulate gyri, insula and thalamus in all groups. Activation of volitional swallowing in dysphagic unilateral hemispheric stroke patients might require reorganisation of the dominant hemispheric motor cortex, or a compensatory shift in activation to unaffected areas of the hemisphere.
The results indicate that unilateral stroke of either cerebral hemisphere can produce dysphagia. Effective recovery is associated with cerebral activation related to cortical swallowing representation in the compensating or recruited areas of the intact hemisphere. Functional MRI is a useful method for exploring the spatial localisation of changes in neuronal activity during tasks that may be related to recovery. Therefore, the subsequent information gleaned from changes in neural plasticity could be useful for assessing the prognosis of dysphagic stroke.
To test the hypothesis that diffuse abnormalities precede axonal damage and atrophy in the MRI normal-appearing tissue of relapsing-remitting (RR) multiple sclerosis (MS) patients, and that these processes continue during clinical remission.
Twenty-one recently diagnosed mildly disabled (mean disease duration 2.3 years, mean Expanded Disability Status Scale score of 1.4) RR MS patients and 15 healthy matched controls were scanned with MRI and proton MR spectroscopic imaging (1H-MRSI) at 3 T. Metabolite concentrations: N-acetylaspartate (NAA) for neuronal integrity; choline (Cho) for membrane turnover rate; creatine (Cr) and myo-inositol (mI) for glial status were obtained in a 360 cm3 volume of interest (VOI) with 3D multivoxel 1H-MRSI. They were converted into absolute amounts using phantom replacement and normalised into absolute concentrations by dividing by the VOI tissue volume fraction obtained from MRI segmentation.
The patients’ mean VOI tissue volume fraction, 0.92 and NAA concentration, 9.6 mM, were not different from controls’ 0.94 and 9.6 mM. In contrast, the patients’ mean Cr, Cho and mI levels 7.7, 1.9 and 4.1 mM were 9%, 14% and 20%, higher than the controls’ 7.1, 1.6 and 3.4 mM (p = 0.0097, 0.003 and 0.0023).
The absence of early tissue atrophy and apparent axonal dysfunction (NAA loss) in these RR MS patients suggests that both are preceded by diffuse glial proliferation (astrogliosis), as well as possible inflammation, demyelination and remyelination reflected by elevated mI, Cho and Cr, even during clinical remission and despite immunomodulatory treatment.
Hypointense lesions on T1 weighted MRI, referred to as black holes (BH), are a marker of demyelination/axonal loss in multiple sclerosis (MS). There is some evidence that glatiramer acetate (GA) may decrease the conversion of new brain lesions to BH.
Monthly 3-Tesla brain MRI scans were used for up to 2 years to study the development and evolution of new BH in 75 patients with MS randomised to GA or Interferon β-1b (IFNβ1b) in the BECOME study.
Of 1224 newly enhancing lesions (NEL) appearing at baseline through 24 months in 61 patients, 767 (62.7%) showed an acute BH (ABH). The majority of ABH were transient and of similar duration by treatment group. Of 571 ABH in which MRI follow-up scans were available for >=1 year, 103 (18.8%) were still visible >=12 months after onset and were considered chronic BH (CBH). Only 12.1% of the 849 NEL with MRI follow-up >=1 year converted to CBH, 9.8% with IFNβ1b and 15.2% with GA (p = 0.02). The conversion from ABH to CBH was also lower with IFNβ1b (15.2%) than with GA (21.4%), of borderline significance (p = 0.06). The majority of patients who developed NEL did not develop CBH; however, about a quarter had conversion rates from ABH to CBH greater than 20%.
Only a minority of new brain lesions in patients with MS treated with GA or IFNβ1b convert to CBH.
In the pathology of sporadic inclusion body myositis (sIBM), the relevance of cell stress molecules such as the heat shock protein B-crystallin, particularly in healthy appearing muscle fibres, has remained elusive.
10 muscle biopsies from sIBM patients were serially stained for haematoxylin–eosin, trichrome and multi-immunohistochemistry for neural cell adhesion molecule (NCAM), B-crystallin, amyloid precursor protein (APP), desmin, major histocompatibility complex I, β-amyloid and ubiquitin. Corresponding areas of all biopsies were quantitatively analysed for all markers. Primary myotube cultures were exposed to the proinflammatory cytokines interleukin (IL)-1β and interferon (IFN)-.
In human myotubes exposed to IL-1β+IFN-, overexpression of APP was accompanied by upregulation of B-crystallin. In sIBM muscle biopsies, over 20% of all fibres displayed accumulation of β-amyloid or vacuoles/inclusions. A clearly larger fraction of the fibres were positive for B-crystallin or APP. In contrast with the accumulation of β-amyloid in atrophic fibres, a major part of fibres positive for APP or B-crystallin showed no morphological abnormalities. Expression of APP and B-crystallin significantly correlated with each other and most double positive fibres displayed accumulation of β-amyloid, vacuoles or an atrophic morphology. In almost all of these fibres, other markers of degeneration/regeneration such as NCAM and desmin were evident as additional indicators of a cell stress response. Some fibres double positive for APP and B-crystallin displayed infiltration by inflammatory cells.
Our results suggest that B-crystallin is associated with overexpression of APP in sIBM muscle and that upregulation of B-crystallin precedes accumulation of β-amyloid. The data help to better understand early pathological changes and underscore the fact that a network of cell stress, inflammation and degeneration is relevant to sIBM.
The use of diffusion tensor imaging with three-dimensional fibre tracking (DTI-FT) was tested for the assessment of spinal sensory tract lesions. The relationships between tract lesions quantified with DTI-FT were systematically examined, and somatosensory dysfunction was assessed with quantitative sensory testing (QST) and laser-evoked potentials (LEP), in patients with syringomyelia.
28 patients with cervical syringomyelia and thermosensory impairment of the hands, and 19 healthy volunteers, were studied. A DTI-FT of the spinal cord was performed, focusing on the upper segment (C3–C4) of the syrinx. Three-dimensional DTI-FT parameters (fractional anisotropy (FA) and apparent diffusion coefficient (ADC)) of the full, anterior and posterior spinal cord were individually compared with QST (thermal detection thresholds) and LEP (amplitude, latency and spinothalamic tract (STT) conduction time) of the hands.
Patients had a significantly lower FA, but not ADC, than healthy subjects. The mean FA of the full section of the spinal cord was correlated both to sensory deficits (ie, increase in warm (rho = –0.63, p<0.010) and cold thresholds (rho = –0.72; p<0.001 of the hands)) and to changes in LEP parameters, in particular STT conduction time (rho = –0.75; p<0.010). Correlations between FA and the clinical and electrophysiological measures were higher in the anterior area (where the spinothalamic tracts are located) than in the posterior area of the spinal cord.
The data indicate that diffusion tensor imaging with 3D-fibre tracking is a new imaging method suitable for the objective and quantitative anatomical assessment of spinal somatosensory system dysfunction.
Muscle weakness is a potentially important, yet poorly studied, risk factor for falls. Detailed studies of patients with specific myopathies may shed new light on the relation between muscle weakness and falls. Here falls in patients with facioscapulohumeral disease (FSHD) who suffered from lower limb muscle weakness were examined. This study provides insights into the prevalence, relevance and pathophysiology of falls in FSHD.
A validated questionnaire was used as well as a prospective 3 month follow-up to examine the prevalence, circumstances and consequences of falls in 73 patients with FSHD and 49 matched healthy controls. In a subgroup of 28 subjects, muscle strength was also examined and balance was assessed electrophysiologically using body worn gyroscopes.
In the questionnaire, 30% of the patients reported falling at least once a month whereas none of the controls did. Injuries occurred in almost 70% of the patients. The prospective study showed that patients fell mostly at home, mainly due to intrinsic (patient related) causes, and usually in a forward direction. Fallers were unstable while climbing stairs, rising from a chair and standing with eyes closed whereas non-fallers had normal balance control. Frequent fallers had greater muscle weakness than infrequent fallers.
These findings demonstrate the high prevalence and clinical relevance of falls in FSHD. The relation between muscle weakness and instability among fallers is also highlighted. Because patients fell mainly at home, fall prevention strategies should focus on home adaptations. As mainly intrinsic causes underlie falls, the impact of adopting balance strategies or balance training should be explored in this patient group.
Diagnostic criteria for chronic inflammatory demyelinating polyneuropathy (CIDP) have variable sensitivity and specificity. Newly published criteria by Koski et al combine clinical and electrophysiological components, either of which suffices to establish the diagnosis. European Federation of Neurological Societies/Peripheral Nerve Society (EFNS/PNS) criteria require mandatory electrophysiology, as do other sets of criteria.
The value of the two above-mentioned sets of criteria, on 151 patients with CIDP, and 162 controls with axonal neuropathy, from four European centres was assessed. Results were compared with Van den Bergh and Piéret’s criteria and those of the American Academy of Neurology (AAN). The utility of more extensive nerve-conduction studies was ascertained.
Koski et al’s criteria had a sensitivity of 63% and specificity of 99.3%. With unilateral, right-sided, forearm/foreleg, four-nerve studies, EFNS/PNS criteria offered a sensitivity of 81.3% and specificity of 96.2% for "definite/probable" CIDP. Van den Bergh and Piéret’s criteria had a sensitivity of 79.5% and specificity of 96.9%. AAN criteria were poorly sensitive (45.7%) but highly specific (100%). "Possible" electrophysiological CIDP as per EFNS/PNS criteria were poorly specific (69.2%). More extensive studies increased the diagnostic sensitivity of EFNS/PNS criteria (96.7%) but reduced the specificity (79.3%).
In our patient populations, the EFNS/PNS criteria were the most sensitive and allowed identification of a highly significantly greater number of patients than Koski et al’s criteria. The latter were comparable in specificity with the "definite/probable" EFNS/PNS electrodiagnostic subcategories. More extensive nerve-conduction studies improved diagnostic yield but resulted in loss of specificity.
Provocative clinical tests are often performed in the diagnosis of ulnar neuropathy at the elbow (UNE) although the evidence for the usefulness of these tests is limited. The aim of this study was to determine the diagnostic value of provocative clinical tests in the diagnosis of UNE in a relevant spectrum of patients and controls.
A prospective cohort study was performed in consecutive patients clinically suspected of having UNE. All patients underwent a neurological examination and four commonly used provocative clinical tests (Tinel’s test, flexion compression test, palpating for local ulnar nerve tenderness and nerve thickening). Subsequently, in all patients a reference standard test comprising electrophysiological studies and neurosonography was independently assessed.
192 eligible patients completed the study protocol. UNE was diagnosed in 137 and an alternative diagnosis was made in 55 patients. The sensitivity, specificity, and positive and negative predictive values were as follows: Tinel’s test 62%, 53%, 77% and 30%; flexion compression test 61%, 40%, 72% and 29%; palpating for nerve thickening 28%, 87%, 84% and 33%; and palpating for nerve tenderness 32%, 80%, 80% and 32%. Logistic regression and receiver operating characteristic curves showed that the added value of one or more provocative tests over routine clinical examination is minimal.
The diagnostic value of provocative clinical tests in UNE is poor.
Lateral spread response (LSR) to the electrical stimulation of a facial nerve branch is a specific electrophysiological feature of primary hemifacial spasm (HFS). The curative treatment of HFS is based on surgical microvascular decompression (MVD). However, the outcome of this procedure is not always satisfactory.
To evaluate the correlation between intraoperative LSR changes and the short- and long-term postoperative clinical outcome following MVD.
Thirty-two consecutive patients with primary HFS treated by MVD performed with intraoperative LSR monitoring were retrospectively included. The patients were assessed for the presence of HFS and surgical complications at 1 day, 1 month and 6 months after surgery. The long-term clinical result was assessed between 1 and 10 years (mean 5.4 years) using a self-report questionnaire.
Patients were divided into three groups based on intraoperative LSR changes: (1) in 15 patients, LSRs were present before incision and disappeared after MVD (47%); (2) in nine patients, LSRs were present before incision but persisted despite MVD (28%); (3) in eight patients, LSRs were absent before surgery and remained so after the procedure (25%). Intraoperative LSR abolition during the MVD procedure correlated with HFS relief in the long term (p<0.0001, Fisher exact test), but not on the first day after surgery (p = 0.3564).
Monitoring MVD by recording LSRs intraoperatively could be of value not only to indicate the resolution of the vasculonervous conflict at the end of surgery, but also to predict a successful clinical outcome in the long term after the surgical intervention.
There are currently no data available on drain associated infection occurrence related to the number of drainage days (DD), and thus drain associated infection rates. Therefore, a prospective surveillance study was conducted to determine drain associated infection rates and DD of hospital acquired external ventricular drain (EVD) and lumbar drain (LD) associated meningitis/ventriculitis in a neurosurgery and a neurological intensive care unit.
All patients admitted in 2005 and 2006 were documented. Data on age, admitting diagnosis, type and duration of drain, duration of hospital stay and occurrence of meningitis were recorded and analysed statistically.
A total of 1333 patients were included, amounting to 3023 DD. After exclusion of 15 contaminations, a total of 26 cases of meningitis were reported accounting for an overall device associated meningitis rate of 8.6 infections/1000 DD. Infections associated with LD seemed to occur more frequently (19.9/1000 DD) compared with EVD (6.3/1000 DD). The presence of intraventricular blood and previous trauma were significant risk factors for infection (p = 0.003; p = 0.04). Finally, length of stay was significantly longer in meningitis patients (p = 0.0003). Coagulase negative staphylococci were the main pathogen (56%) causing meningitis, followed by Staphylococcus aureus (25%).
To the best of the authors' knowledge, this study represents the first to provide data on EVD as well as LD associated meningitis rates calculated per 1000 DD; a parameter that is well established for other invasive devices such as central venous and urinary tract catheters. However, further prospective studies are needed to investigate the possible risk factors for meningitis.
Acute brainstem infarction with basilar artery (BA) occlusive disease is the most fatal type of all ischaemic strokes. This report investigates the prognostic impact of the posterior communicating artery (PcoA) and whether its anatomy is a safeguard or not.
Consecutive patients who had acute brainstem infarction with at least 50% stenosis of BA upon CT angiography (CTA) were studied. The configuration of PcoA was divided into two groups upon CTA: "textbook" group (invisible PcoA with good P1 and P2 segment) and "fetal-variant of PcoA" group (only visible PcoA with absent P1 segment). Baseline demographics, radiological findings and stroke mechanisms were analysed. A multiple regression analysis was performed to predict clinical outcome at 30 days (modified Rankin disability Scale (mRS<=2)).
Among all 95 patients, 58% (n = 55) had good prognoses (mRS<=2). Interestingly, 44 patients (46.3%) had at least one fetal-variant PcoA (26 bilateral, 18 unilateral). By multiple logistic regression analysis, the atherosclerotic mechanism (OR 18.0; 95% CI 3.0 to 107.0) and presence of fetal-variant PcoA (OR 5.1; 95% CI 1.4 to 18.8) were independent predictors for good prognosis and initial NIH stroke scale score (OR 1.24 per one-point increase; 95% CI 1.1 to 1.4) for poor prognosis.
Fetal-variant PcoA appears to act as a safeguard against ischaemic insult in acute stroke victims involving the brainstem with BA occlusive disease. This result can be explained by the fact that patients with fetal-variant PcoA have a smaller area of posterior circulation and a possibility of retrograde filling into the upper brainstem through the fetal-variant PcoA.
Patients with a history of subarachnoid haemorrhage (SAH) may be at risk for vascular events and excess mortality.
We interviewed 752 patients (mean age 50 years, 67% women, mean follow-up 8.1 years) clipped between 1985 and 2001 after SAH who had been discharged home or to a rehabilitation facility about new vascular events. We compared age- and sex-specific mortality after SAH with that of the general population by standardised mortality ratios (SMR). The incidence of vascular events in SAH patients was compared with that in patients after a transient ischaemic attack or minor stroke.
The SMR for SAH patients was 1.7 (95% CI 1.4 to 2.1) overall and 3.2 (95% CI 0.8 to 13.1) for patients <40 years. In the first 10 years after SAH the cumulative incidence of a vascular event was 11.2% (95% CI 7.0 to 14.4), which was lower (hazard ratio 0.43, 95% CI 0.33 to 0.57) than that in patients with a minor stroke.
SAH patients who recover to a functional independent state have an excess mortality compared with the general population. The risk of vascular events after SAH is lower than after minor stroke, but higher than the population risks reported in the literature.
Hereditary spastic paraplegias (HSP) are clinically and genetically highly heterogeneous. Recently, two novel genes, SPG11 (spatacsin) and SPG15 (spastizin), associated with autosomal recessive HSP, were identified. Clinically, both are characterised by complicated HSP and a rather similar phenotype consisting of early onset spastic paraplegia, cognitive deficits, thin corpus callosum (TCC), peripheral neuropathy and mild cerebellar ataxia.
To compare the frequency of SPG11 and SPG15 in patients with early onset complicated HSP and to further characterise the phenotype of SPG11 and SPG15.
A sample of 36 index patients with early onset complicated HSP and a family history compatible with autosomal recessive inheritance was collected and screened for mutations in SPG11 and SPG15. Overall frequency of SPG11 was 14% (5/36) but was considerably higher in patients with TCC (42%). One patient with mental retardation and thinning of the corpus callosum was compound heterozygous for two novel SPG15 mutations. Additionally, several new polymorphisms and sequence variants of unknown significance have been identified in the SPG15 gene.
TCC seems to be the best phenotypic predictor for SPG11 as well as SPG15. No clinical features could discriminate between SPG11 and SPG15. Therefore, priority of genetic testing should be driven by mutation frequency that appears to be substantially higher in SPG11 than in SPG15.
Limb-girdle muscular dystrophy 2I (LGMD2I) is caused by mutations in the fukutin-related protein gene FKRP, which is also involved in congenital muscular dystrophy (MDC1C).
To evaluate the clinical, biological, radiological and mutational characteristics of LGMD2I patients with FKRP mutation.
Eleven patients from nine families from the north of France were studied. Demographical data, muscular testing results, cardiac and respiratory examinations, muscle histological features and a genetic analysis of the FKRP gene for each patient are reported. Eight patients underwent brain MRI and seven neuropsychological tests.
The patients included six women and five men. The mean age at onset was 9 years (range 1.5 to 23 years). Five patients remained self-ambulatory, whereas the other six were confined to a wheelchair by a mean age of 19 years, after a mean disease duration of 10 years. Nine patients suffered from restrictive respiratory insufficiency, and two male patients had severe dilated cardiomyopathy. Neuropsychological tests revealed memory impairment in four cases. Brain MRI revealed cerebral abnormalities in four patients (4/8). Ten patients were carriers of the common L276I mutation, which was either homozygous (four patients) or heteroallelic with another mutation (six patients). Among the mutations found, three were novel: L322V, L489R and R275G.
This study reveals inter- and intrafamilial phenotypic variability in LGMD2I, with a preponderance of myocardiopathy and restrictive respiratory insufficiency. It also demonstrates central nervous involvement, probably associated with changes in -dystroglycan expression in the brain.