Cranial nerve involvement in typical and atypical chronic inflammatory demyelinating polyneuropathies.

BACKGROUND AND PURPOSE: Cranial nerve palsy is occasionally present in patients with chronic inflammatory demyelinating polyneuropathy (CIDP), but its prevalence, characteristics and relations with the CIDP subtypes have rarely been investigated. The aim of this study was to systematically assess cranial nerve involvement in typical and atypical CIDP. METHODS: Clinical data were reviewed in 132 consecutive patients with CIDP, including typical CIDP (n = 89), multifocal acquired demyelinating sensory and motor neuropathy (MADSAM) (n = 31), distal acquired demyelinating symmetric (DADS) (n = 9) and others (n = 3). RESULTS: The frequency of cranial nerve palsy was 11% in typical CIDP, 48% in MADSAM and 11% in DADS. Facial and bulbar palsy was most frequently present (9%), followed by ocular motor nerve palsy (5%). Bilateral involvement was seen in all typical CIDP and DADS patients, whereas 80% of MADSAM patients had unilateral palsy. The presence of cranial nerve involvement was associated with more severe limb muscle weakness in typical CIDP, but not in MADSAM. Cranial nerve palsy fully recovered in 90% of typical CIDP and in 67% of MADSAM patients. CONCLUSION: Amongst the CIDP subtypes, cranial palsy is frequent and unilateral in MADSAM, and less frequent and bilateral in typical CIDP and DADS. In typical CIDP, facial and bulbar palsy reflects more severe and extensive inflammation.

How often and when Fisher syndrome is overlapped by Guillain-Barré syndrome or Bickerstaff brainstem encephalitis?

BACKGROUND AND PURPOSE: Fisher syndrome (FS) may overlap with Guillain-Barré syndrome (GBS), in particular the pharyngeal-cervical-brachial variant form (PCB-GBS), or Bickerstaff brainstem encephalitis (BBE). Our aim was to elucidate the frequency of this overlap and the patterns of clinical progression in patients with FS. METHODS: Sixty consecutive patients with FS were studied. FS/PCB-GBS was diagnosed when the patients developed pharyngeal, cervical and/or brachial weakness. Patients with flaccid tetraparesis were diagnosed as having FS/conventional GBS. FS/BBE was defined as the development of consciousness disturbances. RESULTS: All 60 patients initially developed the FS clinical triad alone (pure FS). Of these, 30 (50%) patients had pure FS throughout their course, whereas the remaining 50% of patients showed an overlap: PCB-GBS in 14 (23%) patients, conventional GBS in nine (15%) patients and BBE in seven (12%) patients. The median (range) durations from FS onset to progression to FS/PCB-GBS, FS/GBS or FS/BBE were 5 (1-7), 3 (1-4) and 3 (1-5) days, respectively. Patients with overlap syndromes more frequently received immune-modulating treatment, and the outcomes were generally favourable. The frequencies of positivity for anti-GQ1b, GT1a, GD1a, GD1b, GalNAc-GD1a and GM1 antibodies were not significantly different amongst the four groups. CONCLUSIONS: Of the patients with pure FS, 50% later developed an overlap with PCB-GBS, conventional GBS or BBE. The overlap occurred within 7 days of FS onset; thus, physicians should pay attention to the possible development of this overlap during the first week after FS onset.

Vascular endothelial growth factor as a predictive marker for POEMS syndrome treatment response: retrospective cohort study.

OBJECTIVE: POEMS (polyneuropathy, organomegaly, endocrinopathy, M-protein and skin changes) syndrome is a rare multisystem disease characterised by plasma cell dyscrasia and overproduction of vascular endothelial growth factor (VEGF). VEGF is assumed to be useful in monitoring disease activity, because VEGF levels usually decrease after treatment. However, there is no study to investigate whether the extent of decrease in VEGF correlates with clinical outcome. We tested the predictive efficacy of serum VEGF levels in POEMS syndrome. METHOD: This was an institutional review board approved retrospective observational cohort study of 20 patients with POEMS monitored regularly for more than 12 months (median follow-up, 87 months) after treatment onset using our prospectively accumulated database of POEMS from 1999 to 2015. Patients were treated by autologous peripheral blood stem cell transplantation or thalidomide administration. Serum VEGF was measured by ELISA. Outcome measures included clinical and laboratory findings and relapse-free survival. RESULTS: Serum VEGF levels decreased rapidly after treatment, and stabilised by 6 months post treatment. Patients with normalised serum VEGF levels (<1040 pg/mL) at 6 months showed prolonged relapse-free survival (HR=12.81, 95% CI 2.691 to 90.96; p=0.0001) and greater later clinical improvement. The rate of serum VEGF reduction over the first 6 months post treatment correlated with increased grip strength, serum albumin levels, and compound muscle action potential amplitudes at 12 months. CONCLUSIONS: Serum VEGF level at 6 months post treatment is a predicative biomarker for disease activity and prognosis in POEMS syndrome. Serum VEGF could be used as a surrogate endpoint for relapse-free survival or clinical or laboratory improvement of POEMS syndrome for clinical trials.

Meropenem as predictive risk factor for isolation of multidrug-resistant Pseudomonas aeruginosa.

The objective of this study was to explore independent risk factors for the isolation of multidrug-resistant (MDR) Pseudomonas aeruginosa in a Japanese university hospital between January 1997 and December 2010. MDR P. aeruginosa was defined when the organism was resistant or intermediately susceptible to all five antimicrobials tested. In all, 159 patients with MDR P. aeruginosa were identified over the 14-year period. Multivariate logistic regression analysis revealed that prolonged hospital stay, prior exposure to meropenem and fluoroquinolones, and patients suffering from diabetes mellitus or receiving surgery were predictive risk factors for the isolation of MDR P. aeruginosa.

Preserved autonomic function in patients with POEMS syndrome.

AIM: We systematically performed autonomic testing on patients with polyneuropathy, organomegaly, endocrinopathy, M-protein and skin changes syndrome (POEMS) to determine whether autonomic function is preserved in such patients. METHODS: We studied 17 POEMS patients, 17 diabetic neuropathy (DN) patients and 17 age-matched normal subjects. Blood pressure responses to the head-up tilt test and heart rate variability were used to evaluate cardiovascular autonomic function. Sweat responses and cutaneous vasoconstriction to several stimuli were recorded via the finger tips to estimate cutaneous sympathetic function. In addition, motor nerve conduction studies were performed. RESULTS: Although the results of the autonomic testing were normal in POEMS patients, motor disability was severe, and motor nerve conduction studies provided evidence of extensive axonal loss. The DN patients showed significantly impaired autonomic responses despite mild motor dysfunction. CONCLUSIONS: Autonomic function was normal in POEMS patients, indicating the preservation of autonomic fibers and selective involvement of large fibers.

Ultrasonographic detection of fasciculations markedly increases diagnostic sensitivity of ALS.

OBJECTIVES: To study the utility of muscle ultrasound (US) for detection of fasciculations and its contribution to diagnosis in amyotrophic lateral sclerosis (ALS). Fasciculations are characteristic features of ALS, and US can detect them easily and reliably. New diagnostic criteria for ALS, the Awaji algorithm, reintroduced fasciculations as evidence of acute denervation equivalent to that of fibrillations and positive sharp waves. METHODS: In 81 consecutive patients with sporadic ALS, we prospectively performed needle EMG and US in 6 muscles (tongue, biceps brachii, first dorsalis interosseous, paraspinalis, vastus lateralis, and tibialis anterior), and diagnostic category were determined by revised El Escorial criteria and Awaji criteria. RESULTS: Fasciculations were much more frequently detected by US than by EMG in the tongue (60% vs 0%), biceps brachii (88% vs 60%), and tibialis anterior muscles (83% vs 45%). The proportion of the patients with definite or probable ALS was 48% by revised El Escorial criteria and 79% by Awaji criteria using US. CONCLUSIONS: Muscle US is a practical and efficient tool to detect fasciculations, particularly in the tongue. A combination of US and EMG substantially increases the diagnostic sensitivity of ALS.

Neuromuscular transmission is not impaired in axonal Guillain--Barré syndrome.

BACKGROUND: Previous studies have shown that anti-GQ1b antibodies induce massive neuromuscular blocking. If anti-GM1 and -GD1a antibodies have similar effects on the neuromuscular junction (NMJ) in human limb muscles, this may explain selective motor involvement in axonal Guillain--Barré syndrome (GBS). METHODS: Axonal-stimulating single-fibre electromyography was performed in the extensor digitorum communis muscle of 23 patients with GBS, including 13 with the axonal form whose sera had a high titre of serum IgG anti-GM1 or -GD1a antibodies. RESULTS: All patients with axonal or demyelinating GBS showed normal or near-normal jitter, and no blocking. CONCLUSION: In both axonal and demyelinating GBS, neuromuscular transmission is not impaired. Our results failed to support the hypothesis that anti-GM1 or -GD1a antibody affects the NMJ. In GBS, impulse transmission is presumably impaired in the motor nerve terminal axons proximal to the NMJ.

POEMS syndrome with Guillan-Barre syndrome-like acute onset: a case report and review of neurological progression in 30 cases.

POEMS (polyneuropathy, organomegaly, endocrinopathy, M-protein and skin changes) syndrome is a rare cause of demyelinating neuropathy with monoclonal plasma cell proliferation, and POEMS neuropathy is usually chronically progressive. Herein, the authors report a 34-year-old woman with POEMS syndrome presenting as acute polyneuropathy. Within 2 weeks of disease onset, she became unable to walk with electrodiagnostic features of demyelination and was initially diagnosed as having Guillan-Barré syndrome. Other systemic features (oedema and skin changes) developed later, and an elevated serum level of vascular endothelial growth factor led to the diagnosis of POEMS syndrome. She received high-dose chemotherapy with autologous peripheral blood stem cell transplantation, resulting in good recovery. The authors also reviewed patterns and speed of progression of neuropathy in the 30 patients with POEMS syndrome; 22 (73%) of them were unable to walk independently with the median period of 9.5 months from POEMS onset (range 0.5-51 months). Whereas the speed of neuropathy progression varies considerably among patients, some POEMS patients can show acute or subacute polyneuropathy. The early diagnosis and treatment could result in rapid improvement as shown in the present patient.

Spinal myoclonus in the periscapular muscles after mastectomy assessed by FDG-PET.

We describe a 64-year-old woman who developed spinal myoclonus around the left scapula after long thoracic nerve injury by mastectomy. Involuntary muscle twitching was semi-rhythmic, and ultrasonography identified contraction of the serratus anterior, teres major, and rhomboid muscles. FDG-PET imaging revealed markedly increased glucose uptake only in the serratus anterior. Lidocaine injection into this muscle resulted in complete cessation of the involuntary movement, and then she was successfully treated with botulinum toxin type A. These findings raise the possibility that the myoclonus was primarily caused by ectopic firing of the injured long thoracic nerve, then spreading to adjacent muscles possibly via a central mechanism mediated by group Ia afferents. The new imaging tools, such as FDG-PET and ultrasonography, were useful to determine the therapeutic target muscle.

Neurologic improvement after peripheral blood stem cell transplantation in POEMS syndrome.

BACKGROUND: Polyneuropathy, organomegaly, endocrinopathy, M-protein, and skin changes (POEMS) syndrome is a rare multisystem disorder associated with plasma cell dyscrasia. There is increasing evidence that high-dose chemotherapy with autologous peripheral blood stem cell transplantation (Auto-PBSCT) is an efficacious treatment. OBJECTIVE: To elucidate the extent and time course of neurologic improvement after Auto-PBSCT in patients with POEMS syndrome. METHODS: Clinical and electrophysiologic findings in nine patients were reviewed. The median follow-up period was 20 months (range, 8 to 49 months). Serum levels of vascular endothelial growth factor (VEGF) were measured by ELISA. RESULTS: Serum VEGF levels rapidly decreased a month after Auto-PBSCT. Within 3 months, neurologic improvement began, and all the patients showed substantial neurologic recovery during the next 3 months. Particularly, three initially chairbound patients regained ability to walk at 6 months. Nerve conduction studies showed significant increases in conduction velocities and amplitudes within 6 months of treatment. At the end of follow-up periods, neuropathy was still improving, and no patients had recurrence of symptoms. CONCLUSION: Autologous peripheral blood stem cell transplantation results in obvious neurologic improvement within 6 months, presumably by extensive axonal regeneration and remyelination. This therapy could be considered as a first line treatment for patients with polyneuropathy, organomegaly, endocrinopathy, M-protein, and skin changes syndrome with younger onset even if they are tetraplegic.

Thalidomide reduces serum VEGF levels and improves peripheral neuropathy in POEMS syndrome.

BACKGROUND: Polyneuropathy, organomegaly, endocrinopathy, M-protein and skin changes (POEMS) syndrome is a rare multi-system disorder associated with plasma-cell dyscrasia. Several case series and reports have suggested that high-dose chemotherapy with autologous peripheral blood stem-cell transplantation is efficacious treatment, but this transplantation is not indicated for elderly patients and patients with renal failure. OBJECTIVE: To investigate the effects of thalidomide treatment for POEMS syndrome. METHODS: Nine patients, who were not indicated for high-dose chemotherapy, were treated with thalidomide. Neurological disability scores, nerve conduction studies and serum levels of vascular endothelial growth factor (VEGF) were prospectively examined. VEGF levels were measured by an enzyme-linked immunosorbent assay. RESULTS: During follow-up periods of 8-23 months (mean, 15 months), all patients showed substantial clinical improvement (n = 6) or stabilisation of symptoms (n = 3). Serum VEGF levels decreased in all patients and were normalised in five patients. Nerve conduction velocities in the median nerve increased in seven patients. There were no serious adverse effects, including thalidomide neuropathy. CONCLUSION: Thalidomide treatment should be further studied as a treatment for POEMS syndrome, particularly for patients who are not indicated for transplantation therapy.

The ipsilateral cortico-spinal tract is activated after hemiparetic stroke.

BACKGROUND AND PURPOSE: The presence of a projection from the primary motor cortex to the ipsilateral muscles has been established in human, but whether this pathway contributes to functional recovery after stroke is unclear. We investigated whether the ipsilateral tract is activated in hemiparetic stroke. METHODS: Motor-evoked potentials (MEPs) were simultaneously recorded from the bilateral trapezius or abductor digiti minimi (ADM) muscles after magnetic stimulation to the motor cortex in 40 acute stroke patients. RESULTS: At rest, ipsilateral trapezius MEPs were recordable in none of the 24 normal controls, and in 38% of the patients after stimulation to the non-affected hemisphere (P < 0.001). With voluntary contraction, ipsilateral trapezius MEPs were elicited in 21% of the normal controls and 73% of the patients (P < 0.001). Ipsilateral ADM MEPs were rarely recordable in both controls (0%) and patients (3%). The presence of ipsilateral trapezius MEPs was associated with less severe paresis in the trapezius (P = 0.04) and deltoid (P = 0.07), but not in the more distal muscles. CONCLUSIONS: The ipsilateral cortico-spinal tract is acutely facilitated after stroke in the trunk or proximal muscles, but not in the hand muscles. Activation of such pathway appears to partly compensate motor dysfunction of the trunk/proximal muscles.

Bickerstaff's brainstem encephalitis and Fisher syndrome form a continuous spectrum: clinical analysis of 581 cases.

Whether Bickerstaff's brainstem encephalitis (BBE) is a distinct disease or a subtype of Fisher syndrome (FS) is unclear as there have been no clinical studies with sufficiently large numbers of patients with FS or BBE. Our aim was to clarify the nosological relationship. Medical records of patients suffering acute ophthalmoplegia and ataxia within four weeks of onset were reviewed. BBE was the diagnosis for patients with impaired consciousness, FS for those with clear consciousness and areflexia. Clinical features, neuroimages, and laboratory findings were analyzed. Patients were grouped as having BBE (n = 53), FS (n = 466), or as unclassified (n = 62). The BBE and FS groups had similar features; positive serum anti-GQ1b IgG antibody (68 % versus 83 %), antecedent Campylobacter jejuni infection (23 % versus 21 %), CSF albuminocytological dissociation (46 % versus 76 %), brain MRI abnormality (11 % versus 2 %), and abnormal EEG findings (57 % versus 25 %). BBE (n = 4) and FS (n = 28) subgroups underwent detailed electrophysiological testing. Both groups frequently showed absent soleus H-reflexes, but normal sensory nerve conduction (75 % versus 74 %) and a 1-Hz power spectrum peak on postural body sway analysis (67 % versus 72 %). Common autoantibodies, antecedent infections, and MRI and neurophysiological results found in this large study offer conclusive evidence that Bickerstaff's brainstem encephalitis and Fisher syndrome form a continuous spectrum with variable CNS and PNS involvement.

Anti-MuSK-positive myasthenia gravis: neuromuscular transmission failure in facial and limb muscles.

The presence of antibodies against muscle-specific receptor tyrosine kinase (MuSK) appears to define a subgroup of patients with myasthenia gravis (MG) characterized by weakness predominant in bulbar, facial and neck muscles compared with anti-acetylcholine receptor (AChR) antibody-positive MG. To investigate the patterns and severity of neuromuscular transmission failure in different muscles in MuSK-positive MG, we performed single fiber electromyography (SFEMG) in the facial (frontalis) and limb (extensor digitorum communis, EDC) muscles in three anti-Musk-positive patients, and compared results with those of 11 anti-AChR-positive patients. Only one of the three MuSK-positive patients had abnormal jitter in EDC, but all the three showed clearly increased jitter in the frontalis. By contrast, the AChR-positive patients showed similarly abnormal jitter for the two muscles. These results suggest that when the diagnosis of anti-MuSK-positive MG is suspected, SFEMG should be performed in most prominently affected muscles.

Aldose reductase inhibition alters nodal Na+ currents and nerve conduction in human diabetics.

BACKGROUND: In diabetic nerves, activation of the polyol pathway via an aldose reductase and the resulting impairment of the Na(+)-K(+) pump would lead to a decreased transaxonal Na+ gradient and thereby reduced nodal Na+ currents. OBJECTIVE: To investigate whether the aldose reductase inhibitor (ARI) epalrestat improves nodal Na+ currents and nerve conduction in human diabetic neuropathy. METHODS: The authors conducted a 6-month, open clinical trial with an ARI, epalrestat, in 30 patients with mild-to-moderate diabetic neuropathy. The latent addition technique and measurements of the strength-duration time constant were used to estimate nodal persistent Na+ currents in median motor axons. Excitability testing and extensive nerve conduction studies including F-wave analyses were performed before and 1 and 6 months after the initiation of treatment with oral epalrestat. RESULTS: Within a month of the start of treatment, there was a significant improvement in nerve conduction, particularly in conduction times across the carpal tunnel and F-wave latencies. The results of latent addition (p < 0.05) and strength-duration time constant (p = 0.06) suggested increased nodal persistent Na+ currents. At 6 months, nerve conduction continued to improve. CONCLUSIONS: Aldose reductase pathway inhibition could rapidly increase nodal Na+ currents and thereby improve the slowing of nerve conduction, presumably because of a restoration of the membranous Na+ gradient.

Abnormal muscle responses in hemifacial spasm: F waves or trigeminal reflexes?

OBJECTIVE: In patients with hemifacial spasm (HFS), abnormal muscle responses (AMR) are frequently present. The objective of this study was to investigate whether the afferent input of AMR is mediated by antidromic facial nerve stimulation or orthodromic trigeminal nerve stimulation. METHODS: AMR in the orbicularis oris muscle were recorded in 28 patients with HFS. When AMR were present, they were recorded after subthreshold stimulation of the facial nerve and weak stimulation delivered to the skin. RESULTS: AMR were recordable in 24 (86%) of the patients, and usually consisted of the early constant component (mean onset latency, 10.0 ms) and late variable component (35.3 ms), similar to R1 and R2 of the blink reflex. The early or late components of AMR, or both, were frequently elicited after subthreshold stimulation of the facial nerve (43%) and skin stimulation (88%). CONCLUSIONS: AMR are likely to be mediated by trigeminal afferent inputs, rather than antidromic activation of the facial nerve, and are a type of trigeminal reflex.