Systematic review of movement disorders and oculomotor abnormalities in Whipple's disease.

Whipple's disease, affecting the CNS, can cause a wide variety of symptoms. Movement disorders are very prevalent, and some are pathognomonic of the disease. This systematic review analyzed all published cases of movement disorders because of CNS Whipple's disease, providing detailed information on clinical and associated features. We have also attempted to address sources of confusion in the literature, particularly related to differing uses of the terminology of movement disorder. This comprehensive overview of Whipple's disease-induced movement disorders aims to aid neurologists in recognizing this very rare disorder and successfully reaching a laboratory-confirmed diagnosis in order to initiate appropriate therapy. © 2018 International Parkinson and Movement Disorder Society.

An atypical limping teenager.

A 13-year-old boy presented with a 5-day history of left-sided limp of gradual onset. There was no history of trauma. He developed a fever and rigours a few days before presenting to the paediatric emergency department. On examination, he was tender on palpating the left gluteal area on active mobilisation of the left hip and could not weight bear on the left leg. Pelvic X-rays and ultrasound of the left hip were normal. The blood results showed raised inflammatory markers and normal white cell count. The blood cultures were positive for Staphylococcus aureus. On day 2, a left hip MRI was performed as well as CT-guided drainage. Diagnosis of left sacroiliac septic arthritis was made. After an initial lack of improvement under intravenous ceftriaxone, a drain was inserted and left in situ for 8 days with double intravenous antibiotic therapy instituted. The patient made a full recovery.

Filterable forms of Nocardia: a preferential site of infection in the mouse brain.

Filterable forms of Nocardia (i.e., filterable nocardiae) are characterized as spherical structures containing many granules. They fluoresce brilliantly under ultraviolet light when stained with acridine orange and are acid-fast in paraffin-containing broth cultures. An accumulation of acid-fast lipochrome bodies, similar to filterable nocardiae, is observed in glial cells of the midbrain nigral lesions found in Parkinson's disease (PD). Preliminary results from experimental infection with filterable nocardiae revealed a possible site of infection in a region of the nervous system associated with movement disorders. Here we examined the preferential site of filterable nocardiae infection in the brain and investigated the effects of various chemicals and biological substances in relation to this preferential site on nocardiae growth in vitro. Examination of tissue samples immunostained for filterable nocardiae revealed that neurons in the olfactory bulbus and the midbrain periaqueductal gray area were immunopositive for filterable nocardiae. Several erythrocytes within blood vessels of the brain were also immunopositive. In addition, a dose-dependent relationship was observed between the growth of filterable nocardiae and erythrocyte lysates. These results suggest first that the preferential site of infection for filterable nocardiae might be erythrocytes, but could also be neurons in the bulbus olfactorius as well as in the midbrain periaqueductal gray area. Second, filterable nocardiae might grow to be branching cylindrical tubules such as that of mycelial bacteria in the presence of erythrocyte lysates.

alpha-Phenyl-n-tert-butyl-nitrone attenuates lipopolysaccharide-induced brain injury and improves neurological reflexes and early sensorimotor behavioral performance in juvenile rats.

Our previous study showed that treatment with alpha-phenyl-n-tert-butyl-nitrone (PBN) after exposure to lipopolysaccharide (LPS) reduced LPS-induced white matter injury in the neonatal rat brain. The object of the current study was to further examine whether PBN has long-lasting protective effects and ameliorates LPS-induced neurological dysfunction. Intracerebral (i.c.) injection of LPS (1 mg/kg) was performed in postnatal day (P) 5 Sprague Dawley rat pups and PBN (100 mg/kg) or saline was administered intraperitoneally 5 min after LPS injection. The control rats were injected (i.c.) with sterile saline. Neurobehavioral tests were carried out from P3 to P21, and brain injury was examined after these tests. LPS exposure resulted in severe brain damage, including enlargement of ventricles bilaterally, loss of mature oligodendrocytes, impaired myelination as indicated by the decrease in myelin basic protein immunostaining, and alterations in dendritic processes in the cortical gray matter of the parietal cortex. Electron microscopic examination showed that LPS exposure caused impaired myelination as indicated by the disintegrated myelin sheaths in the juvenile rat brain. LPS administration also significantly affected neurobehavioral functions such as performance in righting reflex, wire hanging maneuver, cliff avoidance, negative geotaxis, vibrissa-elicited forelimb-placing test, beam walking, and gait test. Treatment with PBN, a free radical scavenger and antioxidant, provided protection against LPS-induced brain injury and associated neurological dysfunction in juvenile rats, suggesting that antioxidation might be an effective approach for therapeutic treatment of neonatal brain injury induced by infection/inflammation.

Spasmodic dysphonia in an adolescent patient with an autoimmune neurologic disorder.

Pediatric autoimmune neuropsychiatric disorder associated with streptococcal infections (PANDAS) has been primarily described in the neurology and psychiatry literature. The symptoms of this syndrome typically are a range of obsessive compulsive disorders and neuromuscular tics. The otolaryngologist occasionally becomes involved with these children when it is deemed that chronic tonsil infections are the source. We report here on a child diagnosed with PANDAS who presented with severe ventricular hyperfunction and adductor spasmodic dysphonia. She was treated with botulinum toxin, which resulted in a significant improvement in subjective voice as well as reduced jitter and shimmer on objective voice measurements.

Antibody-mediated neuronal cell signaling in behavior and movement disorders.

Behavioral and movement disorders may have antibody responses where mimicry and signal transduction may lead to neuropsychiatric abnormalities. In our study, antibodies in pediatric autoimmune neuropsychiatric disorders associated with streptococci (PANDAS) reacted with the neuronal cell surface and caudate-putamen and induced calcium-calmodulin dependent protein (CaM) kinase II activity in neuronal cells. Depletion of serum IgG abrogated CaM kinase II cell signaling and reactivity of CSF was blocked by streptococcal antigen N-acetyl-beta-d-glucosamine (GlcNAc). Antibodies against GlcNAc in PANDAS sera were inhibited by lysoganglioside G(M1). Results suggest that antibodies from an infection may signal neuronal cells in some behavioral and movement disorders.

Anti-basal ganglia antibodies: a possible diagnostic utility in idiopathic movement disorders?

BACKGROUND: The spectrum of post-streptococcal brain disorders includes chorea, tics, and dystonia. The proposed mediators of disease are anti-basal ganglia (neuronal) antibodies (ABGA). AIM: To evaluate ABGA as a potential diagnostic marker in a cohort of UK post-streptococcal movement disorders. METHODS: Forty UK children presenting with movement disorders associated with streptococcal infection were recruited. ABGA was measured using ELISA and Western immunoblotting. To determine ABGA specificity and sensitivity, children with neurological diseases (n = 100), children with uncomplicated streptococcal infection (n = 40), and children with autoimmune disease (n = 50) were enrolled as controls. RESULTS: The mean ELISA result was increased in the post-streptococcal movement disorder group compared to all controls and derived a sensitivity of 82.4% and specificity of 79%. The Western immunoblotting method to detect ABGA derived a sensitivity and specificity of 92.5% and 94.7% respectively. There was common binding to basal ganglia antigens of 40, 45, and 60 kDa. Immunofluorescence localised the antibody binding to basal ganglia neurones. CONCLUSION: ABGA appears to be a potentially useful diagnostic marker in post-streptococcal neurological disorders. Western immunoblotting appears to be the preferred method due to good sensitivity and specificity and the ability to test several samples at once.

Periodic limb movement disorders and spells of profound muscle weakness due to airborne and dietary factors in humans.

Periodic limb movement disorders and the restless legs syndrome, generally considered to be sleep disorders, have a combined prevalence of almost 10% of the general population and are more common in women than in men. Although reduced dopamine activity in central nervous system motor control pathways seems to play a role, little, other than a list of associated risk factors, is known about the conditions that initiate the episodes. We report three patients, two teenage girls and one female teacher, who developed periodic limb movement disorders associated with high mold counts in a classroom and the gymnasium in the girls' school, and in the ventilating system in the teacher's school. Their disorders occurred when they attended their schools and cleared when they did not. These findings, combined with an earlier report of three cases where the disordered movements were triggered by dietary factors, suggest that in some patients, periodic limb movement disorders may be induced by inhalant as well as by dietary factors. Although these 6 patients may represent a subgroup of people with periodic limb movement disorders, potential dietary and environmental triggers should be considered in the clinical evaluation of patients seeking treatment for periodic limb movement disorders.

Neuro-cognitive impairment following acquired central nervous system infections in childhood: a systematic review.

The morbid consequences of central nervous system (CNS) infections are often overlooked in the face of high mortality rates. However, neurological impairments not only affect the child's development and future prospects but also place an economic and social burden on communities and countries that often have few resources to deal with such problems. We conducted a systematic review to investigate the occurrence and pattern of persisting neurological impairment after common CNS infections. A comprehensive search of MEDLINE, EMBASE and PsycINFO databases, supplemented by hand-searches of key journals, resulted in forty-six eligible studies, five of which gave information on the spectrum of developmental domains. Despite the lack of comprehensive, methodologically-sound studies, the results show that postinfectious neurological impairment persists, most commonly in cognition and motor functions. Deficits include more subtle problems, which can be difficult to detect on gross neurological assessment but may still be deleterious to the child's social and educational functioning. Higher morbidity for similar mortality in acute bacterial meningitis compared with cerebral malaria in the epidemiological data may suggest future research directions for clinical research to devise more effective interventions.

Post-streptococcal autoimmune disorders of the central nervous system.

PURPOSE OF REVIEW: Autoimmune disease has long been intertwined with investigations of infectious causes. Antibodies that are formed against an infectious agent can, through the process of molecular mimicry, also recognize healthy cells. When this occurs, the immune system erroneously destroys the healthy cells causing autoimmune disease in addition to appropriately destroying the offending infectious agent and attenuating the infectious process. The first infectious agent shown to cause a post-infectious autoimmune disorder in the central nervous system was Streptococcus pyogenes in Sydenham's chorea. The present review summarizes the most recent published findings of central nervous system diseases that have evidence of a post-streptococcal autoimmune etiology. RECENT FINDINGS: Sydenham's chorea and other central nervous system illnesses that are hypothesized to have a post-streptococcal autoimmune etiology appear to arise from targeted dysfunction of the basal ganglia. PANDAS (pediatric autoimmune disorders associated with streptococcal infections) is the acronym applied to a subgroup of children with obsessive-compulsive disorder or tic disorders occurring in association with streptococcal infections. In addition, there are recent reports of dystonia, chorea encephalopathy, and dystonic choreoathetosis occurring as sequelae of streptococcal infection. Investigators have begun to isolate and describe antistreptococcal-antineuronal antibodies as well as possible genetic markers in patients who are susceptible to these illnesses. SUMMARY: Clinical and research findings in both immunology and neuropsychiatry have established the existence of post-streptococcal neuropsychiatric disorders and are beginning to shed light on possible pathobiologic processes.

Movement disorders in the tropics.

The spectrum of movement disorders in the tropics is different from that seen in the industrialized nations of the west. This is not surprising given the unique combination of environmental and population characteristics in the tropics. Infections seldom encountered in the west such as tuberculous meningitis, typhoid fever, Japanese encephalitis, malaria, trypanosomiasis or cysticercosis are often seen in the tropics and with global patterns of travel and immigration these conditions are becoming more common worldwide. Movement disorders associated with these infections, HIV, slow virus and prion disease are discussed. Taking into account the diverse etiologies of movement disorders in the tropics, movement disorders with a nutritional basis such as the infantile tremor syndrome, seasonal ataxia and tropical ataxic neuropathy, and manganese neurotoxicity are also reviewed. Finally, certain special characteristics of ubiquitous disorders such as Parkinson's disease, and disorders with a genetic basis such as Wilson's disease and spinocerebellar degeneration are described.

Monoamine changes in the brain of BALB/c mice following sub-lethal infection with Nocardia asteroides (GUH-2).

BALB/c mice injected intravenously with a single, sub-lethal dose of Nocardia asteroides GUH-2 develop several levodopa responsive movement disorders. These included headshake, stooped posture, bradykinesia, and hesitation to forward movement. The changes in monoamine levels in the brain of these mice were determined. There was a significant loss of dopamine with greatly increased dopamine turnover in the neostriatum 7 to 29 days after infection. These effects were specific for dopaminergic neurons since minimal changes were found in neostriatal norepinephrine and serotonin even though serotonin turnover was increased. Changes in monoamine metabolism were not limited to the neostriatum. There were reduced levels of serotonin and norepinephrine with increased serotonin turnover in the cerebellum. One year after infection, dopamine metabolism had returned to near normal levels, but many of the movement disorders persisted. Specific changes in neurochemistry did not always appear to correspond with these impairments. Nevertheless, these data are similar to those reported in MPTP treated BALB/c mice.

Movement disorders in encephalitis induced by Rhodococcus aurantiacus infection relieved by the administration of L-dopa and anti-T-cell antibodies.

Mice injected with Rhodococcus aurantiacus by the intravenous (i.v.) route show neurological disorders, hemiparesis, vertical headshake and turn-round gait after day 7 postinfection (p.i.). Neurological symptoms caused by i.v. inoculation of R. aurantiacus were relieved by treatment with levodopa (l-dopa). R. aurantiacus was isolated from the brain and was found to be completely eliminated at day 7 p. i. Focal encephalitis was mainly observed in the brain stem, and T cells could be isolated from the brain after day 7 p.i. Administration of both an anti-CD4 monoclonal antibody (mAb) and an anti-CD8 mAb suppressed neurological symptoms. These results suggest that R. aurantiacus induces movement disorders in mice, and that the symptoms are mediated by T cells infiltrating the brain, rather than directly by the bacterium.

PANDAS: the search for environmental triggers of pediatric neuropsychiatric disorders. Lessons from rheumatic fever.

Pediatric autoimmune neuropsychiatric disorders associated with streptococcal infection (PANDAS) is a relatively new diagnostic construct applied to children or adolescents who develop, and have repeated exacerbations of, tic disorders and/or obsessive-compulsive disorder following group A beta-hemolytic streptococcal infections. The proposed pathophysiology is that the group A beta-hemolytic streptococcal bacteria trigger antibodies that cross-react with the basal ganglia of genetically susceptible hosts leading to obsessive-compulsive disorder and/or tics. This is similar to the etiologic mechanisms proposed for Sydenham's chorea, in which group A beta-hemolytic streptococcal antibodies cross-react with the basal ganglia and result in abnormal behavior and involuntary movements. When first proposed, there was much controversy about the idea that streptococcal infections were etiologically related to rheumatic fever. In a like manner, discussion has arisen about the concept of infection-triggered obsessive-compulsive disorder and tic disorders. We review the historical background to these controversies, give an update on the findings provided by research on PANDAS, and address areas of future study.

Infant botulism. The first culture-confirmed Danish case.

Infant botulism is caused by intestinal colonization by Clostridium botulinum, C. barati or C. butyricum. Infant botulism has only rarely been reported outside the USA. A 3-month-old boy developed constipation, lethargy, feeding difficulties and descending, severe, symmetric weakness. He was breastfed but had also been fed honey. Supportive care led to complete recovery. The serum was positive for C. botulinum toxin type A-F (mouse toxin neutralization assay). A strain of C. botulinum producing toxin type A and E was identified in the stool. C. botulinum was identified in a jar of honey of the same brand as the honey fed to the patient.