Case report: subacute tetraplegia in an immunocompromised patient.

BACKGROUND: Clinical reasoning in Neurology is based on general associations which help to deduce the site of the lesion. However, even "golden principles" may occasionally be deceptive. Here, we describe the case of subacute flaccid tetraparesis due to motor cortical lesions. To our knowledge, this is the first report to include an impressive illustration of nearly symmetric motor cortical involvement of encephalitis on brain MRI. CASE PRESENTATION: A 51 year old immunocompromized man developed a high-grade pure motor flaccid tetraparesis over few days. Based on clinical presentation, critical illness polyneuromyopathy was suspected. However, brain MRI revealed symmetrical hyperintensities strictly limited to the subcortical precentral gyrus. An encephalitis, possibly due to CMV infection, turned out to be the most likely cause. CONCLUSION: While recognition of basic clinical patterns is indispensable in neurological reasoning, awareness of central conditions mimicking peripheral nervous disease may be crucial to detect unsuspected, potentially treatable conditions.

Asymmetric Acute Motor Axonal Neuropathy With Unilateral Tongue Swelling Mimicking Stroke.

A 60-year-old man presented with acute onset of left hemiparesis and left hypoglossal nerve palsy with ipsilateral tongue swelling. He then progressed to tetraparesis in a few days. Cerebrospinal fluid showed cell protein dissociation. A nerve conduction study showed motor axonal neuropathy with sensory sparing. A subsequent blood test revealed anti-GD1b IgG antibody positivity. He was diagnosed to have acute motor axonal neuropathy (AMAN) and treated with a course of intravenous immunoglobulin with slow improvement. This is probably the first AMAN with asymmetrical presentation mimicking stroke reported in the literature in detail. The anti-GD1b IgG antibody is also not commonly associated with AMAN.

Rapidly progressive quadriparesis heralding disseminated coccidioidomycosis in an immunocompetent patient.

Coccidioides species are dimorphic fungi endemic to southwestern USA and northern Mexico. Disseminated coccidioidomycosis is rare with an estimated incidence of 1% in affected individuals and usually presents as meningitis when the central nervous system is involved. Spinal involvement with coccidioidomycosis, though not uncommon, predominantly manifests as osseous involvement leading to osteomyelitis and epidural abscess formation. Progressive quadriparesis as a presenting symptom secondary to intramedullary spinal cord coccidioidomycosis is very unusual and to our knowledge has not been described. We report a patient with disseminated coccidioidomycosis who presented with rapidly progressive quadriparesis due to cervical intramedullary spinal cord involvement. The absence of known coccidioidomycosis with atypical clinical presentation made the diagnosis elusive, requiring emergent cervical laminectomies with dural biopsy for decompression of the spinal cord and confirmation of the diagnosis. The patient eventually succumbed to the progressive course of the disease. Although rare, disseminated coccidioidomycosis can present as new, rapidly progressing quadriparesis in patients who have traveled to endemic areas. A high index of suspicion in such patients with appropriately directed laboratory investigations and consideration of early biopsy might unravel the diagnosis facilitating early antifungal treatment with the potential to minimize morbidity and mortality associated with disseminated coccidioidomycosis.

Mucosal immune responses during court training in elite tetraplegic athletes.

STUDY DESIGN: Experimental study. OBJECTIVES: To examine salivary secretory immunoglobulin A (sIgA) responses and α-amylase activity during court training in highly trained tetraplegic athletes. SETTING: Loughborough, UK. METHODS: Seven highly trained wheelchair rugby athletes with tetraplegia performed two separate wheelchair rugby court training sessions, lasting 23 and 41.5 min, respectively, with either an aerobic or an interval focus. Timed, unstimulated saliva samples were obtained pre, post and 30 min post exercise and analysed for sIgA and α-amylase. Furthermore, blood lactate concentration and rating of perceived exertion (RPE) immediately after training were measured. RESULTS: sIgA secretion rate and α-amylase were unaffected by exercise during both sessions. However, the increases of sIgA concentration (30 min post exercise: +67 ± 29%) during the aerobic session were accompanied by decreases in saliva flow rate (-35 ± 22%). Athletes' physiological responses to exercise document the highly strenuous nature of the sessions, with blood lactate concentrations reaching 8.1 ± 1.0 and 8.7 ± 1.6 mmol l(-1) and RPE reaching 18(17,18) and 16(15,17) for the aerobic and the interval session, respectively. CONCLUSION: Acute bouts of highly strenuous exercise do not have negative impacts on the mucosal immune response in tetraplegic athletes, nor do they influence the production of α-amylase, a marker of sympathetic nervous activity. This contrasts responses previously observed in able-bodied athletes. The disruption of the sympathetic nervous system may prevent the downregulation of sIgA secretion rate following intense exercise, which is a response previously observed in able-bodied athletes.

Salivary immunoglobulin A and upper respiratory symptoms during 5 months of training in elite tetraplegic athletes.

PURPOSE: Altered autonomic innervation in tetraplegic individuals has been shown to depress certain immune parameters at rest and alter exercise-related salivary immunoglobulin A (sIgA) responses. The purpose of this study was to examine resting sIgA responses as a function of training load and episodes of upper respiratory symptoms (URS) in elite tetraplegic athletes. METHODS: Resting saliva samples were obtained from 14 tetraplegic athletes at 12 predefined time points over 5 months and analyzed for sIgA. Occurrence of self-reported URS and training load was recorded throughout the study's duration. Regression analyses were performed to investigate the relationship between sIgA responses and training load. Furthermore, the relationships between sIgA responses and URS occurrence were examined. RESULTS: sIgA secretion rate was negatively correlated with training load (P=.04), which only accounted for 8% of the variance. No significant relationships were found between sIgA responses and subsequent URS occurrence. Finally, sIgA responses did not differ between athletes with and without recorded URS during the study period. CONCLUSIONS: In line with findings in able-bodied athletes, negative relationships between sIgA secretion rate and training load were found in tetraplegic athletes. This may explain some of the higher infection risk in wheelchair athletes with a high training load, which has been previously observed in paraplegic athletes. However, the nonsignificant relationship between sIgA responses and URS occurrence brings into question the use of sIgA as a prognostic tool for the early detection of URS episodes in the studied population.

Downbeat nystagmus, ataxia and spastic tetraparesis due to coeliac disease.

A 25-year-old female presented to a university neurology clinic with a 1-month history of progressive ataxia, downbeat nystagmus and spastic tetraparesis. Personal history revealed polyarthralgias and weight loss. Family history was negative. Following thorough history, laboratory, neurophysiological and MRI investigations, a diagnosis of cerebellar ataxia due to coeliac disease was done. The patient was treated with strict gluten-free diet and intravenous administration of immunoglobulins. Although there are many controversies about neurological manifestations of coeliac disease, this case pointed to strong association between these two disorders. The findings of elevated protein content in the cerebrospinal fluid with positive oligoclonal bands suggested an immune-mediated process, further supported by positive anti-endomysium antibodies and anti-transglutaminase antibodies in the cerebrospinal fluid.

Acute-onset chronic inflammatory demyelinating polyneuropathy with cranial nerve involvement, dysautonomia, respiratory failure, and autoantibodies.

We examined a 27-year-old woman who developed rapidly progressive quadriplegia and acute respiratory failure that required mechanical ventilation in the intensive care unit. It was unclear whether this was a presentation of Guillain-Barré syndrome (GBS) or acute-onset chronic inflammatory demyelinating polyradiculoneuropathy (A-CIDP). Remarkable features included multiple cranial nerve involvement, respiratory failure, dysautonomia, and skin manifestations. Several autoantibodies were elevated, including antinuclear (ANA), anticardiolipin (aCL), thyroid, and calcium-sensing receptor (CaSR) autoantibodies. The patient was initially diagnosed with GBS and treated with intravenous immunoglobulin (IVIg). After almost complete recovery, relapse with quadriplegia and respiratory failure was observed 12 weeks after motor symptom onset. She then received IVIg and steroid pulse therapy followed by maintenance oral methylprednisolone and plasma exchange. She recovered completely 4 months after the relapse. The further clinical and serological course was consistent with systemic lupus erythematosus (SLE)-associated CIDP. Herein we evaluate the association between A-CIDP and some biological markers of autoimmunity.

Association of anti-aquaporin-4 antibody-positive neuromyelitis optica with myasthenia gravis.

We describe 2 patients who developed anti-aquaporin-4 antibody-positive neuromyelitis optica (NMO) following the development of anti-acetylcholine receptor antibody-positive myasthenia gravis (MG). A literature review of 13 similar cases in addition to the present 2 cases of NMO with MG showed predominance among Asian women and frequent development of NMO following thymectomy for MG. Moreover, in one of our patients, serial assays of anti-aquaporin-4 antibody and anti-acetylcholine receptor antibody were performed. Accumulating evidence for the coexistence of NMO and MG suggests that a common immunopathogenesis of NMO and MG may exist, and the association of NMO with MG may be more frequent than hitherto believed.

Low dose HIV-1 Tat improves the defective nuclear factor (NF)-kappaB activity of dendritic cells from persons with spinal cord injury.

Deficits of immune function may be involved in the infections associated with spinal cord injury (SCI). Previous report showed that the impaired maturation potential of dendritic cells (DCs) contributes to immune defect in persons with SCI, especially in those with tetraplegia. To evaluate the roles of cell signaling in the impaired maturation potential of DCs, we assessed the phenotypic and functional maturation potential of DCs in 20 subjects with trauma-induced stable SCI and their neurologically intact healthy control in the presence of DC stimulators, including HIV-1 Tat protein (Tat). Our results showed the tetraplegic subjects had an impaired maturation potential of DCs. The impairment could be attributed to insufficient nuclear factor (NF)-kappaB activity. The maturation potentials and NF-kappaB activity of DCs in response to stimulators could be improved by pretreatment with Tat, although Tat did not increase DC maturation. The improvement by Tat pretreatment was inhibited by a specific NF-kappaB blocker. We concluded that HIV-1 Tat could improve the maturation potentials of DCs from tetraplegic subjects, through Tat-induced enhancement of NF-kappaB activity. These data suggest a potential therapeutic role of HIV-1 Tat in improving immune function in tetraplegic persons.

An unusual complication of immunosuppression in myasthenia gravis: progressive multifocal leukoencephalopathy.

We present a 44-year-old female patient with generalised myasthenia gravis who developed progressive multifocal leukoencephalopathy. She was receiving high dose corticosteroids, azathioprine 200mg daily and high dose intravenous immunoglobulin during relapses. Two months after thymectomy she presented with progressive cognitive decline, asymmetric quadriparesis and ataxia. Two months later she was bedridden. Cranial MRI showed large asymmetric T2 and FLAIR hyperintense lesions in cortical and subcortical structures. Positive CSF PCR of JC virus confirmed the diagnosis. The patient survives with severe sequela which confirms slow progression as typical in nonAIDS cases. This is the second case of progressive multifocal leukoencephalopathy in a myasthenic patient.

Clinical correlates of elevated serum concentrations of cytokines and autoantibodies in patients with spinal cord injury.

OBJECTIVE: To determine the serum cytokine profiles of patients with spinal cord injury (SCI) and varying clinical presentations relative to healthy, able-bodied, age-matched control subjects. DESIGN: Cross-sectional study. SETTING: Clinical research unit. PARTICIPANTS: People with SCI (N=56) and different clinical presentations, and healthy, able-bodied, age-matched control subjects (N=35). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Serum levels of the proinflammatory cytokines interleukin (IL) 1beta, IL-6, tumor necrosis factor alpha (TNF-alpha), the anti-inflammatory cytokines IL-4 and IL-10, the regulatory cytokine IL-2, the IL-1 receptor antagonist (IL-1RA), and autoantibodies against myelin-associated glycoprotein and GM(1) ganglioside (anti-GM(1)) immunoglobulin (IgG and IgM), as determined by enzyme-linked immunosorbent assay. The relationship between elevated serum cytokine levels and clinical variables was also studied. RESULTS: SCI subjects exhibited serum concentrations of IL-6, TNF-alpha, IL-1RA, and anti-GM(1) (IgG) that were greater (P<.05) than control group values. Elevated cytokine concentrations were not associated with high white blood cell counts, level of injury, or American Spinal Injury Association classification; they were evident in SCI subjects who were asymptomatic for medical complications, but were further elevated in subjects with pain, urinary tract infection (UTI), and pressure ulcers. CONCLUSIONS: Elevated levels of circulating proinflammatory cytokines and autoantibodies are present in the serum of SCI subjects without medical complications, and are further elevated in SCI subjects with neuropathic pain, UTI, or pressure ulcers, relative to healthy, able-bodied control subjects. These findings may be indicative of a protective autoimmunity, simply a consequence of occult or evident infection, or evidence of cytokine dysregulation that may contribute to an immune-mediated impairment of axonal conduction.

Chronic inflammatory demyelinating polyneuropathy in a diabetic patient: deterioration after intravenous immunoglobulins treatment and favorable response to steroid treatment.

The authors report the case of a 54-year old type-2 diabetic female patient with a Chronic Inflammatory Demyelinating Polyneuropathy (CIDP). She progressively developed distal hypoesthesia and tetraparesis. She deteriorated after two courses of intravenous immunoglobulins (IVIG) administration and became rapidly wheelchair bound. After one month of steroid treatment, the patient was walking alone. This case raises the question whether IVIG is to be considered as first line treatment for diabetes associated CIDP.

Hepatitis C virus acute quadriparetic vasculitic neuropathy responsive to cyclophosphamide.

PURPOSE: Hepatitis C viral [HCV] infection is a chronic multisystem disorder that may have an indolent course initially. Peripheral neuropathy associated with cryoglobulinemia and a systemic vasculitis is a well-described complication of HCV infection. But this neuropathy is not known to have a late-onset acute fulminant phase. This acute fulminant phase is characterized by quadriparesis associated with pulmonary and/or renal insufficiency, and it may occur despite adequate treatment for HCV infection. The purpose of this study is to report that patients treated for chronic HCV infection may manifest a secondary progressive acute fulminant neuropathy associated with respiratory and/or renal insufficiency that is responsive to cyclophosphamide. METHODS: Case series retrospective data analysis. RESULTS: Three patients with biopsy-proven HCV associated vasculitic neuropathy manifested a secondary progressive acute fulminant course resulting in quadriparesis within 5 years of the initial diagnosis. Complete remission was achieved with cyclophosphamide therapy such that all patients became ambulatory. CONCLUSIONS: HCV-associated vasculitic neuropathy may manifest a secondary phase, which is acute, fulminant and progressive that is superimposed on an otherwise slowly progressive disorder. Cyclophosphamide therapy may abort progression and induce remission of this acute fulminant phase.

Systemic lupus erythematosus presenting as amyotrophic lateral sclerosis.

We report a case of a 27-year-old Omani lady having a 3-year history of progressive skeletal muscle weakness with clinical and skeletal muscle changes of ALS, who during the course of investigations for ALS was found to have SLE. This association is not a simple coincidence but perhaps a causal relationship, opening vistas to explain the autoimmune pathogenesis and justification for immunosuppressive therapy in ALS. SLE presenting as ALS has not been reported earlier.

Mycoplasma pneumoniae causing nervous system lesion and SIADH in the absence of pneumonia.

A patient was admitted for fever and acute respiratory failure (ARF), rapidly progressive tetraparesis, delirium, behavioral abnormalities, and diplopia. Leukocytosis and a rise in C-reactive protein were present. A syndrome of inappropriate anti-diuretic hormone secretion (SIADH) was also diagnosed. Lumbar puncture yielded colorless CFS with mononuclear pleocytosis and protein rise. Electrodiagnosis revealed demyelinating polyneuropathy and axonal degeneration. Serum IgG and IgM for mycoplasma pneumoniae (MP) was consistent with acute infection, and erythromycin was started with rapid resolution of symptoms. Contrarily to most reports, an associated respiratory disease was not present and SIADH in association with MP has been reported only once, in a patient without direct central nervous system (CNS) involvement. Differential diagnosis and possible pathogenic mechanisms are discussed.

Bickerstaff's brainstem encephalitis: clinical features of 62 cases and a subgroup associated with Guillain-Barré syndrome.

Bickerstaff reported eight patients who, in addition to acute ophthalmoplegia and ataxia, showed drowsiness, extensor plantar responses or hemisensory loss. This condition has been named Bickerstaff's brainstem encephalitis (BBE). One patient had gross flaccid weakness in the four limbs. Presumably because of the rarity of this disorder, there has been no reported study on a large number of patients with BBE. To clarify its clinical features, we reviewed detailed clinical profiles and laboratory findings for 62 cases of BBE diagnosed by the strict criteria of progressive, relatively symmetrical external ophthalmoplegia and ataxia by 4 weeks, and disturbance of consciousness or hyperreflexia. Ninety-two per cent of the patients involved had had an antecedent illness. Besides ophthalmoplegia and ataxia, disturbance of consciousness was frequent (74%), and facial diplegia (45%), Babinski's sign (40%) and pupillary abnormality and bulbar palsy (34%) were present. Almost all the patients had a monophasic remitting course and generally a good outcome. Serum anti-GQ1b IgG antibody was positive in 66%, and MRI showed brain abnormality in 30% of the patients. Another striking feature was the association with flaccid symmetrical tetraparesis, seen in 60% of the patients. An autopsy study of a BBE patient clearly showed the presence of definite inflammatory changes in the brainstem: there was perivascular lymphocytic infiltration with oedema and glial nodules. Electrodiagnostic study results suggested peripheral motor axonal degeneration. Limb weakness in the BBE cases studied was considered the result of overlap with the axonal subtype of Guillain-Barré syndrome. These findings confirm that BBE constitutes a clinical entity and provide additional clinical and laboratory features of BBE. A considerable number of BBE patients have associated axonal Guillain-Barré syndrome, indicative that the two disorders are closely related and form a continuous spectrum.