Very early and early neurophysiological abnormalities in Guillain-Barré syndrome: A 4-year retrospective study.

BACKGROUND AND PURPOSE: In its initial stages, Guillain-Barré syndrome (GBS) is difficult to identify, because diagnostic criteria may not always be fulfilled. With this retrospective study, we wanted to identify the most common electrophysiological abnormalities seen on neurophysiological examination of GBS patients and its variants in the early phases. METHODS: We reviewed the clinical records of patients admitted to our Neurology Unit with a confirmed diagnosis of GBS. The study sample was divided in two subgroups according to whether the neurophysiological examination was performed: within 7 days (very early group) or within 7-15 days (early group). H reflex, F waves, and motor and sensory conduction parameters were judged abnormal if they were outside the normal range for at least two nerves. We evaluated neurophysiological findings in Miller-Fisher syndrome (MFS) separately. RESULTS: The study sample comprised 36 patients. In GBS, the most frequent abnormal neurophysiological parameter was the bilateral absence of the H reflex, followed by F wave abnormalities. Motor conduction parameters were altered in less than 50% of patients, and even less common were sensory nerve action potential reduction and the "sural-sparing" pattern. In MFS, H reflex was absent bilaterally in 100% of patients, followed by a predominant peripheral sensory involvement, whereas motor conduction parameters were frequently normal. CONCLUSIONS: Bilateral absence of the H reflex is the most sensitive parameter in early diagnosis of GBS and its variants.

Off-label thrombolysis versus full adherence to the current European Alteplase license: impact on early clinical outcomes after acute ischemic stroke.

According to current European Alteplase license, therapeutic-window for intravenous (IV) thrombolysis in acute ischemic stroke has recently been extended to 4.5 h after symptoms onset. However, due to numerous contraindications, the portion of patients eligible for treatment still remains limited. Early neurological status after thrombolysis could identify more faithfully the impact of off-label Alteplase use that long-term functional outcome. We aimed to identify the impact of off-label thrombolysis and each off-label criterion on early clinical outcomes compared with the current European Alteplase license. We conducted an analysis on prospectively collected data of 500 consecutive thrombolysed patients. The primary outcome measures included major neurological improvement (NIHSS score decrease of ≤8 points from baseline or NIHSS score of 0) and neurological deterioration (NIHSS score increase of ≥4 points from baseline or death) at 24 h. We estimated the independent effect of off-label thrombolysis and each off-label criterion by calculating the odds ratio (OR) with 2-sided 95% confidence interval (CI) for each outcome measure. As the reference, we used patients fully adhering to the current European Alteplase license. 237 (47.4%) patients were treated with IV thrombolysis beyond the current European Alteplase license. We did not find significant differences between off- and on-label thrombolysis on early clinical outcomes. No off-label criteria were associated with decreased rate of major neurological improvement compared with on-label thrombolysis. History of stroke and concomitant diabetes was the only off-label criterion associated with increased rate of neurological deterioration (OR 5.84, 95% CI 1.61-21.19; p = 0.024). Off-label thrombolysis may be less effective at 24 h than on-label Alteplase use in patients with previous stroke and concomitant diabetes. Instead, the impact of other off-label criteria on early clinical outcomes was not different compared with current European Alteplase license.

Androgen-dependent impairment of myogenesis in spinal and bulbar muscular atrophy.

Spinal and bulbar muscular atrophy (SBMA) is an inherited neuromuscular disease caused by expansion of a polyglutamine (polyQ) tract in the androgen receptor (AR). SBMA is triggered by the interaction between polyQ-AR and its natural ligands, testosterone and dihydrotestosterone (DHT). SBMA is characterized by the loss of lower motor neurons and skeletal muscle fasciculations, weakness, and atrophy. To test the hypothesis that the interaction between polyQ-AR and androgens exerts cell-autonomous toxicity in skeletal muscle, we characterized the process of myogenesis and polyQ-AR expression in DHT-treated satellite cells obtained from SBMA patients and age-matched healthy control subjects. Treatment with androgens increased the size and number of myonuclei in myotubes from control subjects, but not from SBMA patients. Myotubes from SBMA patients had a reduced number of nuclei, suggesting impaired myotube fusion and altered contractile structures. The lack of anabolic effects of androgens on myotubes from SBMA patients was not due to defects in myoblast proliferation, differentiation or apoptosis. DHT treatment of myotubes from SBMA patients increased nuclear accumulation of polyQ-AR and decreased the expression of interleukin-4 (IL-4) when compared to myotubes from control subjects. Following DHT treatment, exposure of myotubes from SBMA patients with IL-4 treatment rescued myonuclear number and size to control levels. This supports the hypothesis that androgens alter the fusion process in SBMA myogenesis. In conclusion, these results provide evidence of an androgen-dependent impairment of myogenesis in SBMA that could contribute to disease pathogenesis.

Facial Nerve Neurophysiologic Assessment in Vestibular Schwannoma Removal with Transcanal Approach: A Pilot Clinical Study.

BACKGROUND: The transcanal transpromontorial approach has been introduced to remove vestibular schwannomas. As with other techniques, preservation of the facial nerve (FN) is challenging. This pilot study described FN outcomes of patients preoperatively and postoperatively assessed with electromyography (EMG) and blink reflex (BR). METHODS: Between September 2017 and December 2018, 10 patients (5 men; 5 women; mean age, 59.8 years; age range, 25-77 years) underwent removal of vestibular schwannoma via the transcanal transpromontorial approach. FN assessment using EMG/BR and clinical evaluation with the House-Brackmann (HB) grading scale was performed preoperatively and 2 months postoperatively. If facial impairment was present postoperatively, further analysis was performed 6 months after surgery. RESULTS: All 10 patients had normal FN function on preoperative EMG/BR. After 2 months, 4 patients had normal FN function on EMG/BR, 4 patients showed a slight delay of FN responses, 1 patient had moderate dysfunction, and 1 patient had consistent damage. After 6 months, among the 6 patients with a pathologic neurophysiologic study, consistent EMG/BR improvement was shown, with complete recovery in 3 cases. At the last follow-up, 8 patients had HB grade I, 1 patient had HB grade II, and 1 patient had HB grade III in 1, showing progression toward healing in 9 of 10 cases. CONCLUSIONS: The transcanal transpromontorial approach is an effective procedure for vestibular schwannoma removal. EMG/BR represents an objective evaluation method to verify FN recovery after surgery and confirms the low impact of this surgical procedure on the FN.

Late-onset choreoathetotic syndrome following heart surgery.

Choreoathetotic syndromes are frequently observed in children after congenital cardiopathy surgery. To report the case of an adult patient who developed a choreoathetotic syndrome after cardiac operation, probably related to a transitory hypometabolism of basal ganglia. A 52-year-old patient underwent heart surgery under circulatory arrest and deep hypothermia, for type III dissecting thoracic aorta aneurysm. Two weeks later she developed an acute choreic syndrome. The positron emission tomography using fluorodeoxyglucose (FDGC-PET) showed a bilateral hypometabolism of basal ganglia. After haloperidol administration, choreic syndrome improved and 6 months later FDGC-PET was normal. Choreoathetosis has been described as a rare complication after heart surgery. The authors suggest that this movement disorder may be related to hypothermia that can induce a reversible basal ganglia metabolic damage.

Ifosfamide encephalopathy: a case report.

The aim of this short communication is to discuss the mechanism, modality and treatment of ifosfamide encephalopathy. We present the case of a 52-year-old woman treated with this alkylating agent who developed severe neurotoxicity. It was resolved with administration of Methylene blue, abundant intravenous hydration and interruption of ifosfamide.

Pilot trial of clenbuterol in spinal and bulbar muscular atrophy.

OBJECTIVE: To test the efficacy and tolerability of clenbuterol in patients with spinal and bulbar muscular atrophy (SBMA). METHODS: Twenty patients with a diagnosis of SBMA were given oral clenbuterol (0.04 mg/d) for 12 months. The primary efficacy end point was the change from baseline of the walking distance covered in 6 minutes at 12 months. Secondary end points included the change over time in muscle strength assessed with the Medical Research Council scale, the revised Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS-R), and forced vital capacity values. Safety was assessed by a series of laboratory and instrumental tests, as well as reporting of adverse events. RESULTS: Sixteen patients completed the study. There was a significant and sustained increase in walking distance covered in 6 minutes and forced vital capacity between the baseline and the 12-month assessments (p < 0.001). No differences were recorded in Medical Research Council or ALSFRS-R scores between baseline and follow-up assessments. Serious side effects, including those on heart function, were absent. A significant increase in serum creatine kinase levels was observed. CONCLUSIONS: Our findings suggest a positive effect of clenbuterol on SBMA disease progression. CLASSIFICATION OF EVIDENCE: This study provides Class IV evidence that clenbuterol is effective in improving motor function in SBMA.

Pisa syndrome without neuroleptic exposure in a patient with Parkinson's disease: case report.

We report on a patient affected by Parkinson's disease who developed over a period of a few weeks a tonic deviation of her head, neck, and trunk fitting the typical description of Pisa syndrome (PS). This patient was under stable levodopa and pramipexole treatment and had never been exposed to any psychotropic or antiemetic drugs before or at the time she developed the postural abnormality. Because dopamine transporter imaging revealed bilateral and symmetrical reduction of striatal uptake, we suggest that PS is not primarily related to side differences in dopaminergic denervation or drug exposure.

Long-lasting modulation of human motor cortex following prolonged transcutaneous electrical nerve stimulation (TENS) of forearm muscles: evidence of reciprocal inhibition and facilitation.

Several lines of evidence indicate that motor cortex excitability can be modulated by manipulation of afferent inputs, like peripheral electrical stimulation. Most studies in humans mainly dealt with the effects of prolonged low-frequency peripheral nerve stimulation on motor cortical excitability, despite its being known from animal studies that high-frequency stimulation can also result in changes of the cortical excitability. To investigate the possible effects of high-frequency peripheral stimulation on motor cortical excitability we recorded motor-evoked potentials (MEPs) to transcranial magnetic stimulation (TMS) of the left motor cortex from the right flexor carpi radialis (FCR), extensor carpi radialis (ECR), and first dorsal interosseous (FDI) in normal subjects, before and after transcutaneous electrical nerve stimulation (TENS) of 30 min duration applied over the FCR. The amplitude of MEPs from the FRC was significantly reduced from 10 to 35 min after TENS while the amplitude of MEPs from ECR was increased. No effects were observed in the FDI muscle. Indices of peripheral nerve (M-wave) and spinal cord excitability (H waves) did not change throughout the experiment. Electrical stimulation of the lateral antebrachial cutaneous nerve has no significant effect on motor cortex excitability. These findings suggest that TENS of forearm muscles can induce transient reciprocal inhibitory and facilitatory changes in corticomotoneuronal excitability of forearm flexor and extensor muscles lasting several minutes. These changes probably may occur at cortical site and seem to be mainly dependent on stimulation of muscle afferents. These findings might eventually lead to practical applications in rehabilitation, especially in those syndromes in which the excitatory and inhibitory balance between agonist and antagonist is severely impaired, such as spasticity and dystonia.

Botulinum toxin for the treatment of genital pain syndromes.

Our purpose was to test the effect of botulinum toxin injections on hypertonic pelvic floor muscles of patients suffering from genital pain syndromes. We report two cases of women complaining of a genital pain syndrome resistant to pharmacological therapies and rehabilitation exercises associated with a documented involuntary tonic contraction of the levator ani muscle as a defense reaction triggered by vulvar pain. We performed botulinum toxin injections into the levator ani with the intent to relieve pelvic muscular spasms. Within a few days after the injections both the patients reported a complete resolution of the painful symptomatology, lasting for several months. Our experience suggests that botulinum injections are indicated in patients with genital pain syndrome with documented pelvic muscle hyperactivity, whose symptoms arise not only from genital inflammation and lesions, but also, and sometimes chiefly, from levator ani myalgia.

Impaired heteronymous somatosensory motor cortical inhibition in dystonia.

A typical pathophysiological abnormality in dystonia is cocontraction of antagonist muscles, with impaired reciprocal inhibitory mechanisms in the spinal cord. Recent experimental data have shown that inhibitory interactions between antagonist muscles have also a parallel control at the level of the sensorimotor cortex. The aim of this work was to study heteronymous effects of a median nerve stimulus on the corticospinal projections to forearm muscles in dystonia. We used the technique of antagonist cortical inhibition, which assesses the conditioning effect of median nerve afferent input on motor evoked potentials (MEPs) elicited by transcranial magnetic stimulation (TMS) in ipsilateral forearm extensor muscles at rest. Nine healthy subjects and 10 patients with torsion dystonia participated in the study. MEPs and somatosensory evoked potentials were normal in patients. In healthy subjects, median nerve stimulation at 15- to 18-msec intervals inhibited the test MEPs in forearm extensors. In dystonic patients, median nerve stimulation delivered at the same conditioning-test intervals elicited significantly less inhibition of the test MEP. On the whole, these data suggest an impaired sensory-motor integration in dystonia and, more specifically, the decreased antagonistic cortical inhibition could suggest that functional interactions between antagonist muscles are primarily impaired at the cortical level.