Longstanding spastic paraparesis in a patient infected with hepatitis C virus and seropositive for aquaporin-4 antibody - Case report and review of the literature.

Nervous system involvement in Hepatitis C virus infection (HCV) has been associated to neuro-immunological deregulation, particularly in interferon-alpha treated patients. We present a case of optic and brainstem demyelinating disorder associated with aquaporin-4 (AQP4) antibodies. A 48 year-old woman, with previous diagnosis of non-treated hepatitis C, presented with a 10-year history of long-standing gait disturbance. Neurological examination disclosed a grade 4 spastic paraparesis, lower limb hyperreflexia, right positive Hoffmann sign, bilateral Babinski sign and spastic gait only possible with bilateral support. Spinal cord magnetic resonance imaging (MRI) was normal. Brain MRI showed an asymmetric, bilateral pontine and left mesencephalic hypersignal in T2 and FLAIR, with no gadolinium enhancement. Visual evoked potential revealed bilateral pre-chiasmatic conduction delay. Blood tests showed a positive anti-HCV antibody and a positive AQP4 antibody. Cerebrospinal fluid (CSF) analysis was normal, with no oligoclonal bands. The patient started intravenous (IV) methylprednisolone followed by oral prednisolone; simultaneously, interferon-alpha and ribavirin. There was a slight clinical improvement within the first weeks. There are 7 cases describing association between HCV infection and central nervous system (CNS) demyelination with positive AQP4 antibody, 4 patients under interferon-α. AQP4 antibodies should be tested in patients infected with HCV and CNS demyelination.

Treatment of thyroid-associated orbitopathy with rituximab--a novel therapy for an old disease: case report and literature review.

OBJECTIVE: To report the use of rituximab to treat thyroid-associated orbitopathy (TAO) in a patient with a concomitant B-cell organ-specific autoimmune disorder-the stiff person syndrome (SPS). METHODS: We present a case report and a review of the related literature. RESULTS: A 62-year-old man with SPS, latent autoimmune diabetes of the adult, and Graves-Basedow disease was referred to our medical center because of bilateral TAO. An ophthalmologic examination documented asymmetric bilateral NOSPECS (N = no signs or symptoms; O = only signs, no symptoms; S = soft tissue involvement; P = proptosis; E = extraocular muscle involvement; C = corneal involvement; and S = sight loss) class IV TAO (left eye>right eye) with a clinical activity score of 5 on a scale of 7. Magnetic resonance imaging of the orbits documented bilateral exophthalmos (left eye>right eye) due to retrobulbar fibroadipose infiltration, bilateral increase of extrinsic ocular muscle thickness, and enhancement of the left inferior rectus muscle on T2-weighted sequences. Because of concomitant incapacitating SPS and diet-controlled latent autoimmune diabetes of the adult, we excluded long-term corticosteroid therapy as an option and considered the use of rituximab, a mouse-human chimeric monoclonal antibody targeting the CD20 protein on pre-B and mature B lymphocytes. Rituximab was administered in accordance with the protocol for rheumatoid arthritis. During the subsequent 4 months, clinical signs and symptoms of TAO dramatically resolved (clinical activity score = 0 of 7) with a sustained improvement of the spastic paraparesis. The glutamic acid decarboxylase antibody titer remained high, and glycemic control and first-phase insulin secretion did not change. CONCLUSION: Treatment of active TAO with rituximab should be considered when standard intravenous pulse glucocorticoid treatment is contraindicated or ineffective and when SPS or other organ-specific autoimmune disorders with involvement of humoral autoimmunity are present, inasmuch as more than 1 disease may benefit from the use of this chimeric monoclonal antibody.

HTLV-1 infection and the viral etiology of multiple sclerosis.

The HTLV-1 virus produces a progressive inflammatory, and then degenerative, myelopathy which evolves progressively from onset. HTLV-1 in endemic in populations which are recognized as having low risk of multiple sclerosis . Multiple sclerosis generally evolves as a relapsing-remitting disease and affects predominantly Caucasians. In Caucasians, HAM/TSP can be marked by fluctuations as well as relapses. In Asians MS affects preferentially the spinal cord. The author hypothesizes that population selection through environmental factors has pushed the immune response of Caucasians towards generating relapsing-remitting disease and that of Primordial populations towards progressive disease. HTLV-1 endemicity being the marker of Primordial populations and its absence that of Caucasians.

Hypothesis of interference to superinfection between bovine spastic paresis and bovine spongiform encephalopathy; suggestions for experimentation, theoretical and practical interest.

Sub-acute transmissible spongiform encephalopathies (TSEs) or prion diseases are diseases of little known etiology. The origin of these diseases would appear to be an abnormal protease-resistant prion protein (PrP(res)) which would be infectious by directly inducing its defective conformation to the normal native protein (PrP(C)). This hypothesis does not account for certain aspects of TSEs, such as interference to superinfection: in laboratory animals, inoculation by means of an attenuated strain with a long incubation period protects against later infection by a very virulent strain with a short incubation period. The hypothesis is put forward that there exists a possibility of interference to superinfection between neurodegenerative diseases of unknown origin, thought to be similar to TSEs, and a later infection by a TSE. The study of this interference between bovine spastic paresis (BSP) and bovine spongiform encephalopathy (BSE) could be used as a model for this hypothesis. BSP is a very rare disease among cattle, of unknown etiology; it is curable, in the very early stages, by using tryptophan and especially lithium, potentiated by copper and manganese. An etiology close to that of TSEs has been suggested on several occasions. If interference could be demonstrated between BSP and BSE, interesting data would be provided concerning the etiology, the pathogenesis and possibly the treatment and prevention of these diseases. Notably, such data could lead to the development of a treatment and a prevention with lithium and amino acids precursors of neuromediators (tryptophan, tyrosine, glutamic acid, etc.), as well as the developing of a vaccine to combat TSEs, especially BSE and scrapie.

[Neonatal lupus erythematosus and neurologic involvement: an incidental association?]. / Lupus néonatal et atteinte neurologique: une association fortuite?

UNLABELLED: Neonatal lupus erythematosus is a rare disorder characterized by cutaneous lesions of the face and/or congenital heart block. The transplacental transfer of maternal anti-Ro/SSA, anti-La/SSB, or anti-U1RNP antibodies is responsible for the development of the disease. Few cases of neonatal lupus erythematosus with neurological involvement were reported in the medical literature. CASE REPORT: A 36-week GA female infant presented with neonatal lupus erythematosus comprising cutaneous, hematologic and hepatic disorders with a favorable outcome. However, cutaneous atrophy and hyperpigmentation persisted. Spastic paraparesis was diagnosed at the age of six months. CONCLUSION: The neurological lesions in neonatal lupus erythematosus could either be related to the presence of anti-Ro/SSA antibodies of maternal origin, or of anticardiolipin antibodies.