Diagnostic criteria for amyotrophic lateral sclerosis: A multicentre study of inter-rater variation and sensitivity.

OBJECTIVE: This study assesses inter-rater agreement and sensitivity of diagnostic criteria for amyotrophic lateral sclerosis (ALS). METHODS: Clinical and electrophysiological data of 399 patients with suspected ALS were collected by eleven experienced physicians from ten different countries. Eight physicians classified patients independently and blinded according to the revised El Escorial Criteria (rEEC) and to the Awaji Criteria (AC). Inter-rater agreement was assessed by Kappa coefficients, sensitivity by majority diagnosis on 350 patients with follow-up data. RESULTS: Inter-rater agreement was generally low both for rEEC and AC. Agreement was best on the categories "Not-ALS", "Definite", and "Probable", and poorest for "Possible" and "Probable Laboratory-supported". Sensitivity was equal for rEEC (64%) and AC (63%), probably due to downgrading of "Probable Laboratory-supported" patients by AC. However, AC was significantly more effective in classifying patients as "ALS" versus "Not-ALS" (p < 0.0001). CONCLUSIONS: Inter-rater variation is high both for rEEC and for AC probably due to a high complexity of the rEEC inherent in the AC. The gain of AC on diagnostic sensitivity is reduced by the omission of the "Probable Laboratory-supported" category. SIGNIFICANCE: The results highlight a need for initiatives to develop simpler and more reproducible diagnostic criteria for ALS in clinical practice and research.

Diffusion-Weighted Zonal Oblique Multislice-EPI Enhances the Detection of Small Lesions with Diffusion Restriction in the Brain Stem and Hippocampus: A Clinical Report of Selected Cases.

Diffusion restriction is the morphologic hallmark of acute ischemic infarcts and excitotoxic brain injury in various cerebral pathologies. Diffusion restriction is visible as hyperintensity on DWI and as hypointensity on ADC maps. Due to the vicinity of multiple anatomic structures in the brain stem and hippocampus, very small lesions with diffusion restriction may result in severe clinical symptomatology, but these small lesions easily go undetected on standard cerebral DWI due to insufficient spatial resolution, T2* blurring, and image artifacts caused by susceptibility-related image distortions. Diffusion-weighted zonal oblique multislice-EPI with reduced FOV acquisition permits a considerable increase in spatial resolution and enhances the visualization of very small pathologic lesions in the brain stem and hippocampus. Improved performance in the depiction of different pathologic lesions with diffusion restriction in the brain stem and hippocampus using this sequence compared with standard DWI in selected cases is presented.

How Common Is Signal-Intensity Increase in Optic Nerve Segments on 3D Double Inversion Recovery Sequences in Visually Asymptomatic Patients with Multiple Sclerosis?

BACKGROUND AND PURPOSE: In postmortem studies, subclinical optic nerve demyelination is very common in patients with MS but radiologic demonstration is difficult and mainly based on STIR T2WI. Our aim was to evaluate 3D double inversion recovery MR imaging for the detection of subclinical demyelinating lesions within optic nerve segments. MATERIALS AND METHODS: The signal intensities in 4 different optic nerve segments (ie, retrobulbar, canalicular, prechiasmatic, and chiasm) were evaluated on 3D double inversion recovery MR imaging in 95 patients with MS without visual symptoms within the past 3 years and in 50 patients without optic nerve pathology. We compared the signal intensities with those of the adjacent lateral rectus muscle. The evaluation was performed by a student group and an expert neuroradiologist. Statistical evaluation (the Cohen κ test) was performed. RESULTS: On the 3D double inversion recovery sequence, optic nerve segments in the comparison group were all hypointense, and an isointense nerve sheath surrounded the retrobulbar nerve segment. At least 1 optic nerve segment was isointense or hyperintense in 68 patients (72%) in the group with MS on the basis of the results of the expert neuroradiologist. Student raters were able to correctly identify optic nerve hypersignal in 97%. CONCLUSIONS: A hypersignal in at least 1 optic nerve segment on the 3D double inversion recovery sequence compared with hyposignal in optic nerve segments in the comparison group was very common in visually asymptomatic patients with MS. The signal-intensity rating of optic nerve segments could also be performed by inexperienced student readers.

Phenotypes in Swiss patients with familial ALS carrying TARDBP mutations.

BACKGROUND: Recently, mutations in the TARDBP gene encoding the TAR DNA-binding protein 43 (TDP-43) have been identified in some familial amyotrophic lateral sclerosis (ALS) and sporadic ALS patients. The phenotype and frequency of TARDBP mutation carriers reportedly varies greatly among European populations. OBJECTIVE: To define the phenotypic spectrum of TARDBP mutations and their frequency in a Swiss population. METHODS: A total of 225 patients diagnosed with ALS (182 sporadic cases, 43 familial cases) were screened for TARDBP mutations. All patients were carefully examined and interviewed for a familial predisposition. Except for 1 patient who was followed at the University of Geneva, all patients were followed at the Kantonsspital St. Gallen. RESULTS: 43 patients (19.5%) had a definite family history for ALS. A TARDBP mutation was identified in 4 of these (9.3%). Two female ALS patients carried the p.Asn352Ser mutation. Both had limb onset and a slowly progressive course of the disease. A novel mutation (p.Gly376Asp) was identified in a 44-year-old female patient. Survival amongst affected family members varied between 6 and 18 months. The patient and also the other siblings affected with ALS had an accessory nipple. A fourth male patient carried the p.Ala90Val mutation. None of the patients had overt cognitive impairment. TARDBP mutations were not found among patients with sporadic forms of ALS. CONCLUSION: In this Swiss population, the frequency of familial ALS is higher than reported earlier in other populations. The novel p.Gly376Asp TARDBP mutation is associated with rapid disease progression and may be associated with an accessory nipple while the p.Asn352Ser mutation is associated with slow disease progression.

[The head-up-orthosis - a good solution for ambulant patients with Dropped-head-syndrome]. / Die «Head-Up-Kopfhalteorthese¼ - eine gute Lösung für gehfähige Patienten mit «Dropped-Head-Syndrom¼

Severe paresis of the neck muscles, dystonia or an increased activation of the head flexor can lead to dropped-head syndrome. It can be based on various neurological diseases. We present a patient with amyotrophic lateral sclerosis with severe paresis of the head extensor muscles, which led to a dropped-head syndrome. Usual advices did not permit an adequate swallowing and breathing. The new developed device (head-up) can be adjusted on the individual needs which lead to a marked improvement in quality of life of the patient. Especially for ambulatory patients with Dropped-head syndrome is the «head-up¼ a very good solution.

Limitations of sniff nasal pressure as an outcome measurement in amyotrophic lateral sclerosis patients in a clinical trial.

BACKGROUND: The forced vital capacity (FVC) is an established measure in amyotrophic lateral sclerosis (ALS) clinical trials. Recently the sniff nasal inspiratory pressure (SNIP) test has been increasingly used as a respiratory measure. OBJECTIVES: It was the aim of this study to assess the feasibility of SNIP as an outcome measure in a phase III clinical trial with a lead-in design. METHODS: Twenty patients were enrolled in a randomized clinical trial. FVC, SNIP in sitting (SNIPsitt) and supine (SNIPsup) positions, and the ALS functional rating scale score (ALSFRS-R) were measured every 4 weeks. RESULTS: Complete data were available for 19 patients over 5 months. Baseline values were normal for FVC (101 ± 14%) but abnormal for SNIPsitt and SNIPsup (84 ± 34% and 82 ± 33%). While FVC and ALSFRS-R declined in parallel, SNIPsitt measures declined significantly less compared to ALSFRS-R (p < 0.05) and FVC (p < 0.001) up to 4 months after enrollment. Over 50% of patients still had values equal to or above baseline SNIPsitt measures after 3 months despite abnormal baseline values. CONCLUSIONS: The delayed decline in SNIP measurements suggests a learning effect over time. The optimal number of SNIPs in ALS clinical trials has yet to be determined. SNIP measures should be used with caution in trials with a lead-in design.

[Sensory neuronopathy of Sjögren's syndrome. A diagnostic challenge]. / Sensible Neuronopathie bei Sjögren-Syndrom. Eine diagnostische Herausforderung.

Sjögren's syndrome is an important differential diagnosis in patients with sensory neuronopathy because immunosuppressive therapy may prevent progressive degeneration of sensory fibres, ganglions and axons. Due to the challenges in the diagnostic process the diagnostic criteria have repeatedly changed over the past few years. In patients with negative antibodies (SSA, SSB antibodies) biopsy of the salivary glands of the lip and the parotid gland can be useful to diagnose Sjögren's syndrome. We report on four patients in whom biopsy of the salivary gland was helpful in establishing the diagnosis of Sjögren's syndrome and consequently immunosuppressive therapy was initiated. One of these patients suffered from hypersalivation. This was probably due to denervation hypersensitivity. To our knowledge this has not been reported yet.

[Beware of unconspicious cerebro spinal fluid]. / Gefahrenquelle unauffälliger Liquorstatus.

Nowadays with a lot of diagnostic facilities it is also difficult to find the right diagnose of herpes encephalitis. The aim of this case report was to give an overview about strategies of diagnostic and therapy of the herpes encephalitis.

[Neuroborreliosis--a disease with many faces]. / Die Neuroborreliose - eine Erkrankung mit vielen Gesichtern.

Borreliosis has been widely recognized in Switzerland and is often used in unclear cases with non-specific symptoms. Two illustrative cases should emphasize the current options for diagnosis and therapy of neuroborreliosis. The keystones of the diagnostic instruments are a history with typical symptoms and analysis of the cerebrospinal fluid with determination of appropriate antibodies. Therapy deals with ceftriaxon with intravenous and doxycyclin with oral application making ambulatory treatment possible.

[Psychotic symptoms in a case of locked-in syndrome]. / Psychotische Symptome beim Locked-in-Syndrom.

In this case report we describe a patient who suffered brainstem bleeding mainly in the pons and mesencephalon leading to locked-in syndrome. During rehabilitation she suffered psychotic symptoms of threatening character. Due to location of the lesion and the coincidental appearance of the bleeding, we diagnosed an organic psychosis. After treatment with the atypical neuroleptic drug Quetiapine, the symptoms decreased, facilitating the patient's rehabilitation course.

Modulation of locomotor activity in complete spinal cord injury.

The aim of this study was to evaluate the modulation of muscle activity during locomotor-like movements by different walking speeds in subjects with a motor complete spinal cord injury (SCI) compared to actively--and passively-walking control subjects without neurological deficit. Stepping movements on a treadmill were induced and assisted by a driven gait orthosis. Electromyographic (EMG) muscle activity of one leg (rectus and biceps femoris, tibialis anterior and gastrocnemius) was recorded and analyzed at three stepping velocities with similar body weight support in both subject groups. In SCI subjects, the EMG amplitude of biceps femoris, tibialis anterior and gastrocnemius was in general similar or weaker than in passively- and actively-stepping control subjects, but that of rectus femoris was larger. The degree of co-activation between tibialis anterior and gastrocnemius was higher in SCI than in control subjects. A significant velocity-dependent EMG modulation was present in all four-leg muscles in both subject groups. In SCI subjects, this EMG modulation was similar to that in actively stepping control subjects. It is concluded that in complete spastic SCI subjects, spinal neuronal circuits underlying locomotion can to a large extent adequately respond to a change in external drive to adapt the neuronal pattern to a new locomotion speed. The application of various speeds might enhance the effect of locomotor training in incomplete SCI subjects.