Understanding hyper-reflexia in acute motor axonal neuropathy (AMAN).

Hyper-reflexia is occasionally seen in acute motor axonal neuropathy (AMAN), but its pathophysiology is unclear. We report a patient with AMAN following Campylobacter jejuni enteritis, who showed generalized hyper-reflexia, bilateral Hoffmann sign and right Babinski sign. MRI and transcranial magnetic stimulation of the motor cortex disclosed no corticospinal tract involvement. An extensive electrophysiological investigation documented α-motoneuron hyperexcitability and dysfunction of the interneuronal inhibitory circuits in the spinal anterior horn. We propose an immune-mediated damage of the spinal inhibitory interneuronal network as possible mechanism inducing hyper-reflexia in AMAN.

Anti-Myelin Oligodendrocyte Glycoprotein Antibody Associated With Gray Matter Predominant Transverse Myelitis Mimicking Acute Flaccid Myelitis: A Presentation of Two Cases.

BACKGROUND: Anti-myelin oligodendrocyte glycoprotein (MOG) antibody associated disorders frequently manifest as optic neuritis, transverse myelitis, and acute disseminated encephalomyelitis. While their clinical phenotypes overlap with relapsing inflammatory Central nervous system (CNS) conditions such as multiple sclerosis and neuromyelitis optica spectrum disorder, MOG-related syndromes frequently occur in a younger age group. In children, longitudinally extensive transverse myelitis (LETM) is less specific for anti-aquaporin-4 associated neuromyelitis optica spectrum disorder, and has also been reported in pediatric multiple sclerosis, idiopathic transverse myelitis, and acute flaccid myelitis. METHODS: We summarize two patients with positive MOG antibodies and myelitis. RESULTS: We identified two individuals with anti-MOG associated LETM that demonstrate primarily gray matter involvement. Clinically these patients exhibited hyperreflexia and had rapid improvement with immunotherapies. CONCLUSIONS: Anti-MOG diseases can cause LETM with gray matter predominance mimicking acute flaccid myelitis, but clinically these patients can have retained reflexes and respond favorably to immunotherapies.

Is Ross Syndrome an Autoimmune Entity? A Case Series of 11 Patients.

BACKGROUND: Ross syndrome is diagnosed by the presence of segmental anhidrosis, areflexia, and tonic pupils. Fewer than 60 cases have been described in literature so far. There have been reports of presence of antibodies in such patients, suggesting an autoimmune pathogenesis. METHODS: We describe the clinical profile in this case series of 11 patients with Ross syndrome and discuss the current status of autoimmunity in its pathogenesis and the management. RESULTS: Of the 11 patients with Ross syndrome there was an almost equal sex distribution (male:female ratio was 1.17:1) and the mean age of onset of symptoms was 26 years. Patients took an average of 6 years to present to a tertiary center. Sixty-three percent of the patients presented with complaints of excessive sweating, whereas only 27% had complaints of decreased sweating over a particular area of the body. Only 45% of the patients had the complete triad of Ross syndrome, which included segmental anhidrosis, tonic pupil, and absent reflexes. Eighty-nine percent of the patients had documented absent sympathetic skin response on electromyography. The various markers of autoimmunity were negative in all patients who were investigated for the same in this series. Ninety percent of the patients were managed conservatively. CONCLUSIONS: These findings suggest that, in Ross syndrome, generalized injury to ganglion cells or their projections are not purely autoimmune-mediated.

GD1a-associated pure motor Guillain-Barré syndrome with hyperreflexia and bilateral papillitis.

A patient with acute purely motor polyneuropathy with positive GD1a ganglioside antibodies who presented with paresis in combination with hyperreflexia is reported. Neurophysiological tests revealed features compatible with acute motor axonal neuropathy. Therapy with intravenous immunoglobulin led to rapid clinical improvement. However, at the time when signs of active denervation appeared on electromyographic testing, the patient developed bilateral papillitis. The pathogenesis of pure motor Guillain-Barré syndrome with hyperreflexia and papillitis is discussed.

Stiff person syndrome: presentation of a case with repetitive complex discharges in electromiograms.

INTRODUCTION: Stiff person syndrome is characterized by rigidity of axial and proximal limb muscles, associated with muscle spasms, triggered by unexpected acoustic or somesthetic stimuli. It usually has an autoimmune basis, in which the blood contains antiglutamate decarboxylase antibodies, and is associated with different types of autoimmune diseases. The electromyogram provides evidences of continuous muscular activity. CASE REPORT: A 41-year-old woman with a history of diabetes mellitus type I, Hashimoto thyroiditis, vitiligo, and pernicious anemia developed symptoms compatible with stiff person syndrome. In the electromyogram, in addition to continuous muscular activity, there was evidence of complex repetitive activity in the form of doublets and triplets. CONCLUSIONS: Given the absence of clinical or electrophysiological neuropathic affectation, the presence of doublets and triplets in our patient could be due to a subclinical functional alteration of alpha motoneurons. They could produce the complex repetitive discharges when released from the inhibition mediated by GABAergic neurons.

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.

Isolated abducens nerve palsy as a regional variant of Guillain-Barré syndrome.

The authors reviewed clinical profiles and laboratory findings for 100 cases of abducens nerve paresis without impairment of the other cranial nerves, limb weakness, and ataxia throughout the clinical course. Review of the medical records of 9300 patients referred to our neuoroimmunological laboratory for serum anti-ganglioside antibody testing. Information was obtained from each primary physician on symptoms of preceding infection; initial symptoms; neurological signs during the illness; the clinical course; treatment provided; and outcome. Isolated abducens nerve paresis was present in 100 patients and bilateral paresis in 29. Tentative diagnoses made by the primary physicians on request of anti-ganglioside antibody testing were abducens nerve palsy (n = 68), Fisher syndrome (n = 14), acute ophthalmoparesis without ataxia (n = 14). Symptoms of infection anteceded in 63. Tendon reflexes were absent or decreased in 27. Distal paresthesias were experienced by seven. Serum anti-GQ1b antibody was positive in 25. These findings suggest that some cases of isolated abducens nerve palsy can be categorized as a regional variant of Guillain-Barré syndrome or mild form of Fisher syndrome.

Sequential antibodies to potassium channels and glutamic acid decarboxylase in neuromyotonia.

A patient with thymoma-associated neuromyotonia and voltage-gated potassium channel (Kv1.2 and Kv1.6) antibodies by immunoprecipitation and rat brain immunolabeling was treated successfully with immunoadsorption and cyclophosphamide. Curiously, glutamic acid decarboxylase antibodies, absent at onset, appeared later. Stiff-person syndrome was absent, but fast blink reflex recovery suggested enhanced brainstem excitability. The range of antibodies produced in thymoma-associated neuromyotonia is richer, and the timing of antibody appearance more complex, than previously suspected.

Bickerstaff's brainstem encephalitis associated with IgM antibodies to GM1b and GalNAc-GD1a.

This is the first report of a case of Bickerstaff's brainstem encephalitis (BBE) associated with IgM antibodies to GM1b and GalNAc-GD1a. Subsequent to Campylobacter jejuni enteritis, the patient rapidly developed consciousness disturbance and hyperreflexia in addition to external ophthalmoplegia and cerebellar-like ataxia. EEG showed transient 7 Hz monorhythmic theta activities, predominantly in the front-central area. He received high doses of immunoglobulin intravenously and had completely recovered 3 months later. High anti-GM1b and anti-GalNAc-GD1a IgM antibody titers present during the acute phase decreased with his clinical improvement. An absorption study showed the anti-GM1b and anti-GalNAc-GD1a IgM antibodies to be cross-reactive. Anti-GM1b and anti-GalNAc-GD1a antibodies have been detected in some patients who developed Guillain-Barré syndrome after C. jejuni enteritis, whereas the anti-GQ1b IgG antibody is associated with BBE. Infection by C. jejuni bearing a GM1b-like or GalNAc-GD1a-like lipooligosaccharide may trigger the production of anti-GalNAc-GD1a and anti-GM1b IgM antibodies. It is not clear why our patient developed BBE rather than Guillain-Barré syndrome. These antibodies may, however, prove useful serological markers for identifying BBE patients who do not have the anti-GQ1b IgG antibody.

Human T-cell lymphotropic virus type I (HTLV-I)-related clinical and laboratory findings for HTLV-I-infected blood donors.

Clinical and laboratory findings were examined for 111 human T-cell lymphotropic virus type I (HTLV-I)-infected blood donors. HTLV-I provirus loads in subjects with a family history of adult T-cell leukemia (ATL) or HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP) tended to be higher than those in subjects without a family history of these conditions. There were 3 asymptomatic patients with ATL, 4 with a history of uveitis, 7 with hyperreflexia in the lower limbs, and 3 with urinary frequency in the night. The mean CD4 cell/CD8 cell ratio +/- SD was significantly lower (p<.0001) in subjects with hyperreflexia in the lower limbs (1.3 +/- 0.2) than in subjects without any clinical abnormalities (1.7 +/- 0.6), suggesting that subjects with hyperreflexia in the lower limbs already have some immunologic abnormalities. The concordance of HTLV-I infection between husband and wife was lower in this study than in a previous study. HTLV-I-related inflammatory symptoms were more frequent (p =.021, Fisher exact test; OR = 9.5; 95% CI, 1.7-53.5) in HTLV-I tax A-infected donors (3 [50%] of 6 donors) than in HTLV-I tax B-infected donors (10 [9.5%] of 105 donors), suggesting different risks of HTLV-I-related symptoms according to the virus genotype.

Association of autonomic nervous hyperreflexia and systemic inflammation in patients with Crohn's disease and ulcerative colitis.

The autonomic nervous system modulates gastrointestinal motility, secretion and mucosal immunity. Its dysfunction may be of pathogenetic importance in inflammatory bowel disease (IBD). This study aimed at investigating the autonomic nervous function in patients with IBD. Forty-seven patients with IBD, 28 with Crohn's disease (CD) and 19 with ulcerative colitis (UC), were investigated by means of 5 cardiovascular and 2 pupillary standardized autonomic nervous function tests. In CD and UC, cardiovascular autonomic neuropathy was very rare (0%, 5%), whereas pupillary autonomic neuropathy was more prevalent (21%, 21%). In contrast to autonomic neuropathy, overall cardiovascular (CD: 29%, UC: 26%) and pupillary autonomic hyperreflexia (46%, 37%) were found more often. Patients with CD and UC demonstrated elevated percentiles in the respiratory sinus arrhythmia test as compared to controls (RSA: 82.3 +/- 3.9%, 80.0 +/- 5.9%, controls: 50.0% +/- 1.5%, p < 0.0001). CD patients with, as compared to patients without, RSA hyperreflexia had significantly higher CDAIs (p < 0.001), increased erythrocyte sedimentation rates (p < 0.005) and more often extraintestinal disease manifestations (p < 0.001). UC patients with, as compared to patients without, pupillary latency time hyperreflexia had lower hemoglobin (p < 0.05), lower albumin (p < 0.01) and increased erythrocyte sedimentation rates (p < 0.05). Autonomic hyperreflexia was significantly associated with more severe inflammation and systemic disease in IBD. Hyperreflexia may be a response to inflammation or a pathogenetic element that drives mucosal inflammation.

Serum antibodies against gangliosides and Campylobacter jejuni lipopolysaccharides in Miller Fisher syndrome.

Seven patients with Miller Fisher syndrome (MFS), six in the acute phase and one in the recovery phase, were investigated for serum antibodies against gangliosides and purified lipopolysaccharides (LPS) from different strains of Campylobacter jejuni, including the MFS-associated serotypes O:2 and O:23. Immunoglobulin G antibodies against gangliosides GT1a and GQ1b were found in five of six patients in the acute phase of disease. Three of these patients also displayed antibodies to ganglioside GD2, a finding not previously reported for MFS. All anti-GT1a- and anti-GQ1b-seropositive patients showed antibody binding to C. jejuni LPS, predominantly to O:2 and O:23 LPS. Antibody cross-reactivity between gangliosides GT1a and GQ1b and O:2 and O:23 LPS was demonstrated by adsorption studies. This cross-reactivity between gangliosides and C.jejuni LPS, which is obviously due to oligosaccharide homologies, may be an important pathogenetic factor in the development of MFS after C. jejuni infection.

[The detection of anti-cerebellar antibody western blot analysis in serum from a patient with Miller Fisher syndrome].

We here report a case of Miller Fisher syndrome (MFS) in which serum anti-cerebellar antibody was detected by Western blot analysis. The 32-year-old male studied suffered from diplopia, gait ataxia and sensory disturbance in the distal portion of the upper limbs preceded by cold-like symptoms. Neurological examination on admission revealed that he had external ophthalmoplegia with bilateral ptosis, cerebellar ataxia and areflexia. A cerebrospinal fluid examination showed albuminocytologic dissociation with a protein concentration of 60 mg/dl. Brain CT and MRI showed no significant abnormalities. The patient was diagnosed as MFS, and treated it with two sessions of immunoadsorption plasmapheresis (IAPP). After receiving IAPP therapy, the patient's neurological symptoms and signs were improved. Western blot analysis showed the existence of antibody directed against mouse cerebellum but not against mouse cerebrum, brain stem, and spinal cord in his serum, the level of which was decreased after the IAPP therapy. Serum anti-GQ1b antibody was also elevated. As far as we are aware, there have been no reports showing the existence of anti-cerebellar antibodies detected by Western blot analysis. Though the pathogenesis of MFS remains unclear, our findings suggest that anti-cerebellar antibody detected by Western blot analysis may be caused by cerebellar ataxia in MFS.

Acute ataxic neuropathy with cross-reactive antibodies to GD1b and GD3 gangliosides.

We report a patient with an acute, self-limiting neuropathy consisting of ataxia and areflexia, but without ophthalmoplegia or limb weakness, with transient, high-titer serum IgG antibodies to a single NeuAc(alpha 2-8)NeuAc-linked disialosyl epitope, as found on GD1b and GD3 gangliosides. The serum did not react with GQ1b, GT1a, or GT1b. This atypical case, which most closely represents an incomplete Miller Fisher syndrome, indicates that anti-GD1b/GD3 antibodies may be able to induce sensory ataxia.