Bickerstaff Brainstem Encephalitis and overlapping Guillain-Barré syndrome in children: Report of two cases and review of the literature.

Bickerstaff Brainstem Encephalitis (BBE) is a rare autoimmune encephalitis, characterized by acute ophthalmoplegia, ataxia and altered state of consciousness. Together with Guillan-Barrè Syndrome (GBS) and Miller-Fisher Syndrome, it forms a spectrum of post-infectious demyelinating diseases. Overlapping forms between BBE and GBS (BBE/GBS) are described in patients with lower limbs weakness and typical signs of BBE, suggesting a combined involvement of Central and Peripheral Nervous System (PNS), but only few reported cases are focused on pediatric population. We reviewed all cases of pediatric BBE in the literature, to determine if any patient showed features suggestive for BBE/GBS. Data analysis focused on the diagnostic tests performed (e.g. anti-GQ1b antibodies), neuroimaging and nerve conduction studies (NCS). Further attention was given to the therapeutic management and to patients' outcome. We additionally present two previously unreported pediatric cases. Our review retrieved 19 cases of BBE/GBS, only 2 of which were originally and correctly diagnosed by the authors. The prevalence was higher in male subjects (ratio 3:1) and median age at diagnosis was 8 years. Anti-GQ1b were positive in 46% of the patients, while NCS were altered in 64%. Only 25% of the patients that underwent brain MRI showed abnormal findings. The incidence of BBE/GBS has been underrated in the past, mostly due to an underestimation of the PNS involvement. We therefore suggest to investigate all patients with a clinical picture suggestive of BBE/GBS through electroencephalogram, NCS, brain and spine MRI in order to promptly achieve the correct diagnosis.

Laryngeal and phrenic nerve involvement in a patient with hereditary neuropathy with liability to pressure palsies (HNPP).

Lower cranial and phrenic nerve involvement is exceptional in hereditary neuropathy with liability to pressure palsies (HNPP). Here we report the occurrence of reversible laryngeal and phrenic nerve involvement in a patient with HNPP. The patient recalled several episodes of reversible weakness and numbness of his feet and hands since the age of 30 years. His medical history was uneventful, apart from chronic obstructive pulmonary disease (COPD). At age 44, following severe weight loss, he presented with progressive dysphonia and hoarseness. EMG of cricoarytenoid and thyroarytenoid muscles and laryngeal fibroscopy confirmed vocal cord paralysis. These speech disturbances gradually regressed. Two years later, he reported rapidly worsening dyspnea. Electroneurography showed increased distal latency of the right phrenic nerve and diaphragm ultrasonography documented reduced right hemi-diaphragm excursion. Six months later and after optimization of CODP treatment, his respiratory function had improved and both phrenic nerve conduction and diaphragm excursion were completely restored. We hypothesize that chronic cough and nerve stretching in the context of CODP, together with severe weight loss, may have triggered the nerve paralysis in this patient. Our report highlights the need for optimal management of comorbidities such as CODP as well as careful control of weight in HNPP patients to avoid potentially harmful complications.

Combined central and peripheral demyelination: Clinical features, diagnostic findings, and treatment.

Combined central and peripheral demyelination (CCPD) is rare, and current knowledge is based on case reports and small case series. The aim of our study was to describe the clinical features, diagnostic results, treatment and outcomes in a large cohort of patients with CCPD. Thirty-one patients entered this retrospective, observational, two-center study. In 20 patients (65%) CCPD presented, after an infection, as myeloradiculoneuropathy, encephalopathy, cranial neuropathy, length-dependent peripheral neuropathy, or pseudo-Guillain-Barré syndrome. Demyelinating features of peripheral nerve damage fulfilling European Federation of Neurological Societies/Peripheral Nerve Society (EFNS/PNS) electrodiagnostic criteria for CIDP were found in 23 patients (74%), and spatial dissemination of demyelinating lesions on brain MRI fulfilling the 2010 McDonald criteria for multiple sclerosis (MS) in 11 (46%). Two thirds of the patients had a relapsing or progressive disease course, usually related to the appearance of new spinal cord lesions or worsening of the peripheral neuropathy, and showed unsatisfactory responses to high-dose corticosteroids and intravenous immunoglobulins. The clinical presentation of CCPD was severe in 22 patients (71%), who were left significantly disabled. Our data suggest that CCPD has heterogeneous features and shows frequent post-infectious onset, primary peripheral nervous system or central nervous system involvement, a monophasic or chronic disease course, inadequate response to treatments, and a generally poor outcome. We therefore conclude that the current diagnostic criteria for MS and CIDP may not fully encompass the spectrum of possible manifestations of CCPD, whose pathogenesis remains largely unknown.

Monitoring effectiveness and safety of Tafamidis in transthyretin amyloidosis in Italy: a longitudinal multicenter study in a non-endemic area.

Tafamidis is a transthyretin (TTR) stabilizer able to prevent TTR tetramer dissociation. There have been a few encouraging studies on Tafamidis efficacy in early-onset inherited transthyretin amyloidosis (ATTR) due to Val30Met mutation. However, less is known about its efficacy in later disease stages and in non-Val30Met mutations. We performed a multi-center observational study on symptomatic ATTR patients prescribed to receive Tafamidis. We followed up patients according to a standardized protocol including general medical, cardiological and neurological assessments at baseline and every 6 months up to 3 years. Sixty-one (42 males) patients were recruited. Only 28 % of enrolled subjects had the common Val30Met mutation, mean age of onset was remarkably late (59 years) and 18 % was in advanced disease stage at study entry. Tafamidis proved safe and well-tolerated. One-third of patients did not show significant progression along 36 months, independently from mutation type and disease stage. Neurological function worsened particularly in the first 6 months but progression slowed significantly thereafter. Autonomic function remained stable in 33 %, worsened in 56 % and improved in 10 %. Fifteen percent of patients showed cardiac disease progression and 30 % new onset of cardiomyopathy. Overall, Tafamidis was not able to prevent functional progression of the disease in 23 (43 %) subjects, including 16 patients who worsened in their walking ability and 12 patients who reached a higher NYHA score during the follow-up period. A higher mBMI at baseline was associated with better preservation of neurological function. In conclusion, neuropathy and cardiomyopathy progressed in a significant proportion of patients despite treatment. However, worsening of neurological function slowed after the first 6 months and also subjects with more advanced neuropathy, as well as patients with non-Val30Met mutation, benefited from treatment. Body weight preservation is an important favorable prognostic factor.

Double innervation in free-flap surgery for long-standing facial paralysis.

OBJECTIVE: One-stage free-flap facial reanimation may be accomplished by using a gracilis transfer innervated by the masseteric nerve, but this technique does not restore the patient's ability to smile spontaneously. By contrast, the transfer of the latissimus dorsi innervated by the contralateral facial nerve provides the correct nerve stimulus but is limited by variation in the quantity of contraction. The authors propose a new one-stage facial reanimation technique using dual innervation; a gracilis muscle flap is innervated by the masseteric nerve, and supplementary nerve input is provided by a cross-face sural nerve graft anastomosed to the contralateral facial nerve branch. METHODS: Between October 2009 and March 2010, four patients affected by long-standing unilateral facial paralysis received gracilis muscle transfers innervated by both the masseteric nerve and the contralateral facial nerve. RESULTS: All patients recovered voluntary and spontaneous smiling abilities. The recovery time to voluntary flap contraction was 3.8 months, and spontaneous flap contraction was achieved within 7.2 months after surgery. According to Terzis and Noah's five-stage classification of reanimation outcomes, two patients had excellent outcomes and two had good outcomes. CONCLUSIONS: In this preliminary study, the devised double-innervation technique allows to achieve a good grade of flap contraction as well as emotional smiling ability. A wider number of operated patients are needed to confirm those initial findings.

Choosing the best rehabilitation treatment for Bell's palsy.

BACKGROUND: It is useful to perform neurophysiologic electromyography and electroneurography (EMG/ENG) on patients with peripheral facial palsy during the acute phase of paralysis in order to assess the severity of their nerve lesion and thus plan rehabilitation treatment and evaluate its results. AIM: To evaluate the motor recovery of patients with Bell's palsy with respect to the severity of their neurological lesion and to compare the results of two different rehabilitation treatments, with electromyographic biofeedback (EMG-BFB) and mirror visual biofeedback (mirror-BFB), in patients with Bell's palsy and neurophysiologic pattern of axonotmesis. STUDY DESIGN: Cohort study on retrospective clinical records. POPULATION: 102 patients with Bell's facial palsy were clinically assessed according to the House scale both during the acute phase of paralysis and 12 months after onset. METHODS: All patients underwent EMG/ENG examination 3-4 weeks after the onset of paralysis; 29 patients had an EMG pattern of neurapraxia and were not given rehabilitation treatment; 73 patients who presented with signs of denervation had an EMG pattern of axonotmesis. The group, which was homogenous in terms of lesion severity, was divided into two parts: 38 patients were treated with electromyographic biofeedback (EMG-BFB) and 35 were treated with mirror visual feedback (mirror-BFB). RESULTS: All 29 patients with neurapraxia made a full spontaneous recovery; Although the 73 patients with axonotmesis received different types of rehabilitation treatment, they obtained similar results regarding quality of recovery, development of synkinesis, rehabilitation timing and resources used. CONCLUSION AND CLINICAL REHABILITATION IMPACT: Rehabilitation treatment is not necessary for patients with neurapraxia. The two biofeedback methods used to treat patients with axonotmesis resulted in similar rehabilitation outcomes.

An electrophysiological approach to the diagnosis of neurogenic dysphagia: implications for botulinum toxin treatment.

OBJECTIVES: Botulinum toxin (BTX) injection into the cricopharyngeal (CP) muscle has been proposed for the treatment of neurogenic dysphagia due to CP hyperactivity. The aim was to determine whether an electrophysiological method exploring oropharyngeal swallowing could guide treatment and discriminate responders from non-responders, based on the association of CP dysfunction with other electrophysiological abnormalities of swallowing. METHODS: Patients with different neurological disorders were examined: Parkinson disease, progressive supranuclear palsy, multiple system atrophy-Parkinson variant, multiple system atrophy cerebellar variant, stroke, multiple sclerosis and ataxia telangiectasia. All patients presented with clinical dysphagia, and with complete absence of CP muscle inhibition during the hypopharyngeal phase of swallowing. Each patient underwent clinical and electrophysiological investigations before and after treatment with BTX into the CP muscle of one side (15 units of Botox). Clinical and electrophysiological procedures were performed in a blind manner by two different investigators. The following electrophysiological measures were analysed: (1) duration of EMG activity of suprahyoid/submental muscles (SHEMG-D); (2) duration of laryngopharyngeal mechanogram (LPM-D); (3) duration of the inhibition of the CP muscle EMG activity (CPEMG-ID); and (4) interval between onset of EMG activity of suprahyoid/submental muscles and onset of laryngopharyngeal mechanogram (I-SHEMG-LPM). RESULTS: Two months after treatment, 50% of patients showed a significant improvement. Patients with prolonged or reduced SHEMG-D values and prolonged I-SHEMG-LPM values did not respond to BTX. Therefore, values for which BTX had no effect (warning values) were identified. CONCLUSIONS: This electrophysiological method can recognise swallowing abnormalities which may affect the outcome of the therapeutic approach to dysphagia with BTX treatment.

Neurophysiological approach to primary headache pathophysiology.

Electroencephalography (EEG), evoked potentials (EP), and electromyography (EMG) techniques are useful tools in the clinical assessment of headache and in understanding the pathophysiological mechanisms of these pathologies. EEG and EP studies in migraine revealed functional abnormalities in cortical electrical activity and in sensory processing. EMG studies resulted in pain syndromes involving nerves or myofascial structures such as tension-type headache and cluster headache. Moreover, it was possible to test the effect of old and new drugs with the help of these neurophysiological techniques. An updated review is reported of the literature.

Central motor conduction after magnetic stimulation in diabetes.

Central motor conduction times (CMCTs), obtained by means of magnetic stimulation of the motor cortex and spinal roots, were studied in 138 patients affected by diabetes mellitus but with no signs or symptoms of central nervous system (CNS) involvement. CMCTs were significantly increased in diabetic patients (p < 0.001, t-test) with respect to normal controls, with values exceeding upper confidence limits (mean +/- 2.5 SD of controls) in about 30% of patients. There was no correlation between CMCT delay and type of diabetes (insulin-dependent or non-insulin-dependent), patient age, disease duration, degree of metabolic control compensation, presence or absence of retinopathy or nephropathy, and presence or absence of peripheral or autonomic neuropathy. CNS involvement in diabetes mellitus is discussed. Particular emphasis is given to the sensitivity and reliability of CMCTs obtained by means of magnetic stimulation as a tool in the early diagnosis of CNS functional alterations in diabetes mellitus.

Inhibition of the blink reflex R2 component after supraorbital and index finger stimulations is reduced in cluster headache: an indication for both segmental and suprasegmental dysfunction?

Peripheral as well as central mechanisms are thought to play a role in cluster headache pathogenesis. We have studied recovery curves of the R2 component of the blink reflex after conditioning by supraorbital or index finger stimuli in 10 episodic cluster headache (CH) patients during a cluster period and in 10 healthy controls. There was no significant change of R2 threshold, latency or area in CH patients. After paired supraorbital stimuli, R2 recovered more rapidly in patients on the symptomatic side. After index stimulations, R2 recovery was more rapid on both symptomatic and non-symptomatic sides in patients compared to controls. Naloxone (0.4 mg) i.v. in two subjects partially reversed the R2 suppression induced by index finger stimuli. The unilateral decrease of R2 inhibition after a segmental supraorbital stimulus most likely reflects sensitisation in the spinal trigeminal nucleus. Whether the latter is due to irritation of the ophthalmic nerve within the cavernous sinus region, which is thought to be pivotal in CH pathogenesis, remains to be proven. In addition, we propose that the bilateral deficit of R2 inhibition after an extrasegmental exteroceptive stimulus might reflect hypoactivity of reticular nuclei, possibly because of reduced central opioid activity.

Neurophysiological and neuropsychological monitoring of fatigue during extreme environmental and driving conditions.

Aim of the present study was to evaluate the modifications of neurophysiological and neuropsychological variables during extreme environmental and driving conditions. Eight subjects (four drivers and four passengers) were evaluated while driving a four wheels drive across the Big West Algerian Erg. The following procedures were carried out in basal conditions and at the end of the 1st, 3rd, and 5th day of driving: surface EMG of masseter and cervical para-spinal muscles during maximum isometric contraction lasting 12 sec; test of simple visual and acoustic reaction times, Cancellation test, Trial Making test. As from the second day, the drivers used appropriate dental plates. In the drivers, EMG spectrum analysis revealed a significant decrease in mean frequency values at the end of the 1st day. This finding was more relevant in masseter muscles. No significant fatigue phenomena were detected on the subsequent controls. On the contrary, the passengers showed a decrease in mean EMG frequency values. No significant modifications in the cognitive variables were detected at the end of the 1st day (initial response to stress), whereas a progressive worsening was observed in the subsequent evaluations. EMG fatigue of masseter muscles seems to be more related to psychic stress. The beneficial effects of the dental plates were also confirmed.

Functional changes of brainstem reflexes in Parkinson's disease. Conditioning of the blink reflex R2 component by paired and index finger stimulation.

Recovery curves of the R2 component of the blink reflex have been studied in 10 control subjects and 13 parkinsonian patients both after ipsilateral paired stimulation of the supraorbital nerve and after index finger stimulation. In control subjects, both types of conditioning induced a comparable marked inhibition lasting more than 600 ms. In parkinsonian patients, inhibition was reduced after both conditionings. However, differences appeared in the magnitude of the changes: after paired stimulation, it was less significant (ANOVA and post-hoc Duncan's test: p = 0.04) than after index finger stimulation (p = 0.002). In that latter situation, the more marked reduction in inhibition is interpreted, in the light of current physiologic knowledge, by hypoactivity of the Nucleus Reticularis Giganto Cellularis (NRGC) which would make less efficient inhibitory interneurones in the trigemino-facial pathway. The results are thus compatible with the suggestion that NRGC is made indirectly less active in Parkinson's disease.

Twitch response of striated muscle in patients with progressive external ophthalmoplegia, mitochondrial myopathy and focal cytochrome c-oxidase deficiency.

Some aspects of the contractile properties of skeletal muscle in patients with progressive external ophthalmoplegia (PEO), mitochondrial myopathy and focal cytochrome c-oxidase deficiency were investigated by studying the twitch response (TR) of the tibialis anterior muscle both at rest and after maximum isometric contraction. The results of needle electromyography were normal in four of the six examined patients, and myopathic in the remaining two. A slowing in muscle relaxation was the most frequently observed abnormality; significantly prolonged muscle contraction times and reduced twitch torque potentiation values after isometric contraction were also detected. TR abnormalities in PEO patients may be due either to a dysfunction of the contractile machinery depending upon impaired muscle energy supply or to altered muscle fiber characterized by the predominance of type I slow fiber. In addition to conventional electromyographic investigations, TR study may be a useful diagnostic tool in PEO patients.

Electrophysiological study on jaw-opening reflex recorded from digastric muscle in Parkinson's disease and primary cranial dystonias.

We investigated digastric reflex excitability in normals and in patients with extrapyramidal disorders such as primary cranial dystonias and Parkinson's disease. Relationships between exteroceptive suppression of masseter muscle and digastric reflex were also investigated in some cases. Digastric reflex hyperexcitability was observed in dystonic patients when compared to normals and parkinsonian patients. Furthermore, some patients with cranial dystonia presented absence of exteroceptive suppression reflex in masseter muscle with enlarged digastric response. These results indicate hyperexcitability of the digastric reflex and abnormal agonist-antagonist muscle co-contraction in chewing reflexes of patients with cranial dystonias. This shows that digastric reflex is an important electrophysiological investigation to explore the physiopathological mechanisms of primary cranial dystonias.

Local venous lactate changes and spectral analysis of surface EMG during fatiguing isometric efforts in intrinsic hand muscles.

In this study relationships between local venous lactate concentrations and power spectrum changes in surface EMG due to fatiguing isometric contractions were investigated. Two different isometric efforts of the opponents pollicis muscle, 25% and 50% of maximum voluntary contraction, were examined. In 25% of maximum voluntary contraction no changes in local venous lactate were observed, whereas mean power frequency values of surface EMG shifted significantly towards lower frequencies. On the contrary, in 50% of maximum voluntary contraction lactate significantly increased and was related to the mean power frequency shifts of the surface EMG. These data suggest that lactate plays a role in muscle fatigue only in a limited intensity range of isometric muscle contractions.