Annette Baumgartner

Multiple sclerosis rebound following herpes zoster infection and suspension of fingolimod

Fingolimod, a sphingosine 1-phosphate receptor modulator, is highly effective in the treatment of multiple sclerosis (MS).[1][1],[2][2] However, fatal cases of herpes infection have occurred in 2 patients on fingolimod therapy, 1 of whom presented with a primary disseminated varicella-zoster virus (

Immunological findings in psychotic syndromes: a tertiary care hospital's CSF sample of 180 patients

Immunological mechanisms and therapy approaches in psychotic syndromes were recently supported by the discovery of autoantibody-associated limbic and non-limbic encephalitis. However, how clinical diagnostic procedures in psychiatry should be adapted to these new insights is still unclear. In this study, we analyzed the cerebrospinal fluid (CSF) and neuroimmunological alterations and their association with cerebral MRI (cMRI) and electroencephalographic (EEG) findings. From 2006 to 2013, we acquired 180 CSF samples from psychotic patients. Between 2006 and 2009, CSF examinations were only performed in cases in which organic brain disease was suspected. Since then, this procedure has been integrated into our routine diagnostic workup. CSF basic diagnostics were supplemented by measuring antineuronal antibodies against intracellular synaptic antigens, antibodies against intracellular onconeural antigens, antibodies against neuronal cell surface antigens and thyroid antibodies. In addition, cMRIs and EEGs were conducted. We found white cell counts elevated in 3.4% of the cases, albumin quotient elevated in 21.8%, and protein concentration elevated in 42.2%. Evidence of intrathecal immunoglobulin synthesis was found in 7.2% of the cases. Antibodies measured against neuronal cell surface antigens were positive in 3.2%. Reactivity on antibodies against intracellular onconeural antigens were detected in 3.5%. Serum thyroid antibodies were elevated in 24.7%. Abnormalities were found in 39.5% of cMRIs and in 34.3% of EEGs. The main finding of our study was the high prevalence of CSF and autoantibody abnormalities in 54.4% of psychotic patients. In combination with cMRIs and EEGs, 75.6% showed abnormal findings. Our results are discussed with regard to the concept of immunological encephalopathy. Future studies should analyze the efficacy of immunomodulatory therapies.

Severe disease reactivation in four patients with relapsing-remitting multiple sclerosis after fingolimod cessation

OBJECTIVES Fingolimod is a well-established, highly effective immunomodulatory treatment for patients with relapsing-remitting multiple sclerosis (RRMS). However, little is known about disease course after its discontinuation. METHODS This is a case series on four patients with RRMS who had a severe reactivation after fingolimod discontinuation. RESULTS One patient had pretreatment with glatiramer acetate, interferon-β 1b and interferon-β 1a and another with interferon-β 1a, intravenous immunoglobulins and natalizumab whereas the other two were therapy naïve before fingolimod initiation. Patients were treated with fingolimod for two, thirty, forty-five and seventy-eight months, respectively. Fingolimod had to be discontinued because of persisting lymphopenia, severe varicella zoster virus infection, subarachnoid hemorrhage, and increased liver function enzymes, respectively. Between two to four months after fingolimod cessation these patients had a severe relapse. Cerebral magnetic resonance imaging (MRI) at this point revealed multiple new lesions, partially with contrast ring enhancement. Partial recovery was achieved after steroid pulse therapy followed by plasma exchange in two patients. CONCLUSIONS Despite the limited evidence from our case series on potential disease reactivation exceeding pre-fingolimod activity in a subgroup of RRMS patients, particularly patients with previously high disease activity should undergo frequent clinical as well as radiological monitoring after fingolimod discontinuation.

Brain atrophy in pure and complicated hereditary spastic paraparesis: a quantitative 3D MRI study

Hereditary spastic paraparesis (HSP) is a heterogeneous group of neurodegenerative disorders with progressive lower limb spasticity, categorized into pure (p‐HSP) and complicated forms (c‐HSP). The purpose of this study was to evaluate if brain volumes in HSP were altered compared with a control population. Brain volumes were determined in patients suffering from HSP, including both p‐HSP (n = 21) and c‐HSP type (n = 12), and 30 age‐matched healthy controls, using brain parenchymal fractions (BPF) calculated from 3D MRI data in an observer‐independent procedure. In addition, the tissue segments of grey and white matter were analysed separately. In HSP patients, BPF were significantly reduced compared with controls both for the whole patient group (P < 0.001) and for both subgroups, indicating considerable brain atrophy. In contrast to controls who showed a decline of brain volumes with age, this physiological phenomenon was less pronounced in HSP. Therefore, global brain parenchyma reduction, involving both grey and white matter, seems to be a feature in both subtypes of HSP. Atrophy was more pronounced in c‐HSP, consistent with the more severe phenotype including extramotor involvement. Thus, global brain atrophy, detected by MRI‐based brain volume quantification, is a biological marker in HSP subtypes.

Cognitive performance in pure and complicated hereditary spastic paraparesis: a neuropsychological and neuroimaging study

The heterogeneous group of hereditary spastic paraparesis (HSP) is characterized by spastic paraparesis and was classified clinically into pure (pHSP) and complicated (cHSP) subtypes. Whereas cHSP is often associated with cognitive impairment, little is known about the cognitive performance in pHSP. Using a case-control study design, a cohort of 20 pHSP and 9 cHSP patients was assessed neuropsychologically. In the evaluation of working and episodic memory, attention, and executive functions, the cHSP patients showed highly significantly reduced scores in all cognitive domains tested here, whereas no pathological results were observed in the pHSP group. An additional correlation analysis between a 3D magnetic resonance imaging-based calculation of the global brain atrophy and the test performance revealed a strong association for the total HSP group but only weak correlations for the two HSP subtypes. This systematic assessment illustrated the different clinical character of cHSP and pHSP with respect to the cognitive profiles.

Magnetic Resonance Investigation of the Upper Spinal Cord in Pure and Complicated Hereditary Spastic Paraparesis

Neuropathological studies of hereditary spastic paraparesis (HSP) have described axonal loss involving corticospinal and somatosensory tracts in the spinal cord. This MRI-based study was intended to investigate in vivo diameter alterations of the spinal cord in HSP, including both pure HSP (p-HSP, n = 20) and complicated HSP (c-HSP, n = 10). Standard MRI examinations of the cervical and thoracic spinal cord in HSP patients and a control group (n = 54) were analyzed by standardized spinal cord planimetry. In HSP patients, significant atrophy of the upper spinal cord compared to controls was observed at p<0.001 both at the cervical and at the thoracic level. Myelon diameters at both levels were also significantly reduced in the two HSP subgroups in an additional comparison with age-matched subgroups of controls each, but p-HSP and c-HSP groups themselves did not differ. Marked atrophy of the upper spinal cord seems to be associated with HSP, assumedly due to the central-distal axonopathy. However, the differences between p-HSP and c-HSP could not be visualized by structural MRI at spinal cord level.

Anaphylactic reaction after injection of glatiramer acetate (Copaxone®) in patients with relapsing-remitting multiple sclerosis.

ized pruritic exanthema over the whole body immediately after injection of Copaxone. This improved after a few days without therapy and no further symptoms such as dyspnea or hypotension were evident. Following this systemic allergic reaction, therapy with GA was discontinued. Apart from MS, the patient also suffers from recurrent depressive episodes; additional diseases, co-medication or allergies are not evident.

Different regional brain volume loss in pure and complicated hereditary spastic paraparesis: a voxel-based morphometric study.

Three‐dimensional magnetic resonance imaging of the brain was analyzed using optimized voxel‐based morphometry in 21 patients with pure hereditary spastic paraparesis (pHSP) and 12 patients with complicated HSP (cHSP). PHSP patients showed only small regional grey matter volume reduction, whereas significantly decreased grey matter volumes were localized pericentrally in cHSP. In the white matter, several small areas of regional volume reduction were observed in the pHSP patients, whereas the cHSP group exhibited large robust volume reduction involving the entire corpus callosum, a result that was reproduced by an additional region‐based MRI analysis. It could be demonstrated that the topography of cerebral volume changes differed markedly in pHSP or cHSP at group level. Corpus callosum thinning seems to be a general feature of cHSP.

Intrathecal Thyroid Autoantibody Synthesis in a Subgroup of Patients With Schizophreniform Syndromes

Schizophreniform syndromes in combination with autoimmune thyroiditis and increased serum thyroid antibodies lead healthcare practitioners to consider a diagnosis of Hashimotos encephalopathy. To detect specific biomarkers, the authors analyzed whether intrathecal antithyroid antibody synthesis occurred in a subgroup of schizophreniform patients. In doing so, the authors analyzed thyroid antibodies in paired cerebrospinal fluid and serum samples from 100 schizophreniform patients. Increased antibody indices (AIs) for antithyroid peroxidase or antithyroglobulin autoantibodies in 13 schizophreniform patients were found. AIs were increased in 68% of the seropositive patients. These findings support the hypothesis that autoimmune processes may contribute to the pathophysiology in these patients.

The Paroxysmal Disorders

dedicated section), or drop attacks. In addition, despite the ‘updating’ intents, the texts appear at least in part relatively dated. For instance, there is no mention throughout the book about the link between paroxysmal exercise-induced dystonia, glucose transporter (GLUT1) deficiency, and epilepsy (which is known at least since 2008), and the therapeutic role of ketogenic diet. The section on epilepsy treatment does not mention medications marketed since 2006, but reports compounds that are nearly almost forgotten (as tiagabine). Furthermore, one would have expected more emphasis on conditions such as vestibular neuritis, epileptic amnesia, semiology of visual illusions/hallucinations (e.g. the role of color in the differential diagnosis between epileptic and migraine auras, or the superposition on the background for peduncular hallucinosis) and of paresis (e.g. no detailed description of the Hoover sign is found), or epilepsy-induced syncope, which may at times challenge the emergency physician/neurologist. Despite these drawbacks, several book parts are very well written and useful for the clinician, like the headache, the ENT (vertigo), sections of the ophtalmological, and the PNES chapters, while other encompass some details (e.g. epilepsy treatment, stroke diagnosis and treatment) that may go beyond the intent of the editors of this work. In conclusion, despite finding much interesting information, the reader may welcome a truly updated edition of this book, where a general diagnostic overview of paroxysmal conditions (e.g. as a table or flow chart) could also contribute to a more homogeneous and synthetic result, and to an additional usefulness for the clinician. Dr. Andrea O. Rossetti, Lausanne, Switzerland Bettina Schmitz, Barbara Tettenborn, Donald L. Schomer (eds.)