Demyelinating disease (multiple sclerosis) in a patient with psoriatic arthritis treated with adalimumab: a case-based review.

Over the past two decades, tumor necrosis factor-α (TNF-α) inhibitors became one of the most important drugs in the treatment of patients with psoriatic arthritis. Unfortunately, some of the patients exhibit unwanted side effects of the treatment. We describe a patient with psoriasis, psoriatic arthritis and uveitis who was treated with adalimumab and after 4 months of the treatment developed clinical and neuroradiological signs of demyelinating disease of the central nervous system. She experienced no signs and symptoms of neurological disease prior to adalimumab administration. After a detailed neurological work-up she was diagnosed with relapsing-remitting type of multiple sclerosis and treated with oral and pulse glucocorticoids and later with dimethyl fumarate. Adalimumab was discontinued. The question remains was the demyelination induced by the TNF-α blockade or was it unmasked by the introduction of the cytokine blocking agent. In patients suffering from inflammatory arthritis, treating disease to target as well as a close follow-up and knowledge of potential side effects of treatment remains crucial in good clinical practice.

Tongue somatosensory evoked potentials reflect midbrain involvement in patients with clinically isolated syndrome.

AIM: To test the hypothesis that tSSEP findings reflect clinical and MRI MS lesions, the aim of this study was to investigate tSSEP changes in patients with clinically isolated syndrome (CIS) in relation to clinical and brainstem MRI findings. The second aim was to investigate whether the interpretation of the tSSEP results in the form of the tSSEP score enables better evaluation of the afferent trigeminal pathway involvement than analyzing each tSSEP parameter separately. METHODS: 115 consecutive CIS patients were enrolled from August 1, 2014 until March 1, 2016. Facial sensory symptoms and brainstem MRI (1.5 T) lesions were analyzed. tSSEP testing was performed for each patient from the raw tSSEP data. The tSSEP score was calculated separately for the left and right side (according to the cut-off values for absent response and prolonged latency of the main component, P1 (0=normal response, 1=prolonged latency, 3=absent response) and the two values were summed. RESULTS: There was no difference in the absolute values of the tSSEP variables regarding the presence of clinical symptoms. No association was found between tSSEP abnormalities and clinical symptoms (P=0.544). Brainstem lesions (midbrain and pons) were associated with the absent tSSEP responses (P=0.002 and P=0.005, respectively). tSSEP score was significantly higher in patients with brainstem lesions (P=0.01), especially midbrain (P=0.004) and pontine (P=0.008) lesions. Binary logistic regression showed that tSSEP score had a significant effect on the likelihood that patients have midbrain MR lesions, ?2(1)=6.804, P=0.009; and the model correctly classified 87% of cases. CONCLUSIONS: The consistent finding of this study was the association between tSSEP and midbrain lesions on MRI, indicating that tSSEP evaluates proprioception of the face. This study establishes the value of tSSEP in assessing brainstem function in early multiple sclerosis.

Beware of "old" Horner syndrome.

PURPOSE: Chronic Horner syndrome is a rare clinical condition, the etiology of which often remains undiscovered. A patient is presented with an 8-year history of Horner syndrome who was diagnosed with multiple cervical artery dissections. CASE REPORT: A 42-year-old woman presented to our emergency department with a severe occipital headache that woke her up from sleep 3 days earlier. She had a history of headaches and recalled one in particular dating back to 2003. At that time, she sought medical attention at general practitioner's office because of the terrible headache and a noticeable disparity of her pupils. She was told that she had miosis of the right pupil. The examination conducted in 2011 revealed Horner syndrome with right miosis and ptosis. A four-vessel cerebral angiography revealed an occlusion of the right internal carotid artery. The morphology of stenosis and pseudoaneurysm of C1 segment of left internal carotid artery, as well as a pseudoaneurysm of V3/V4 junction of left vertebral artery indicated a probable dissective etiology. CONCLUSIONS: This case illustrates that Horner syndrome with a chronic presentation can be as potentially dangerous as its acute counterpart and should be judiciously investigated.

Brain MRI abnormalities in ataxia-telangiectasia.

BACKGROUND: Ataxia-telangiectasia (AT) is a rare autosomal recessive disorder, initially characterized by normal brain magnetic resonance imaging (MRI). CASE REPORT: In a 34-year-old woman patient with AT, MRI revealed extensive and diffuse white matter dismyelination, T1 and T2 hypointense lesions, T1 hypointense but T2 hyperintense lesions, and numerous dilated telangiectases upon gadolinium enhancement. DISCUSSION: In our patient, brain MRI confirmed extensive extracerebellar lesions in AT. CONCLUSION: Our report broadens the spectrum of brain MRI abnormalities in AT and supports the hypothesis on cerebrovascular abnormalities occurring in later stages of AT.

Isolated cranial nerve palsies in multiple sclerosis.

Data on patients with multiple sclerosis and cranial nerve involvement as a presenting sign or a sign of disease exacerbation were retrospectively analyzed. Isolated cranial nerve involvement was present in 10.4% out of 483 patients, either as a presenting symptom (7.3%) or a symptom of disease relapse (3.1%). Trigeminal nerve was most frequently involved, followed by facial, abducens, oculomotor and cochlear nerves. Only 54% of patients had brainstem MRI lesion that could explain the symptoms. As multiple sclerosis is a disease characterized by multiple neurological symptoms, while early diagnosis and therapy are critical for the prognosis and course of the disease, the diagnosis of multiple sclerosis should be considered in young adults with cranial nerve involvement.

Parkinsonism and multiple sclerosis--is there association?

Association between multiple sclerosis (MS) and parkinsonism is rarely reported. We describe clinical, radiological and DAT scan findings in two patients presenting with parkinsonism. MRI revealed demyelinating lesions of the central nervous system consistent with MS in both patients. On the other hand, DAT scan findings were supportive of Parkinson's disease. There is still an open debate whether MS lesions can cause parkinsonism, or these are just coincidental findings of two different diseases in the same patient. Although there are cases of causal relationship between parkinsonism and MS, some literature reports and our observations suggest that Parkinson's disease and MS can coexist as two separate diseases in the same patient. It is possible that the symptoms of Parkinson's disease can be aggravated by MS plaques, explaining the favorable response to corticosteroids in some patients.

Current concepts in the diagnosis of transverse myelopathies.

The clinical symptoms and MRI characteristics of transverse myelopathy (TM) due to non-compressive causes are reviewed, with special emphasis on the differential diagnosis between inflammatory demyelinating lesions, and metabolic and vascular myelopathies. Inflammatory transverse myelopathies are the commonest and most difficult ones to identify. The differentiation between clinically isolated syndromes, multiple sclerosis, neuromyelitis optica, acute disseminated encephalomyelitis and metabolic causes is based on both clinical symptoms and paraclinical signs including magnetic resonance imaging, cerebrospinal fluid analysis, and immunological and biochemical parameters. The most intriguing form of TM is that where there is clinical evidence of complete spinal cord transection, with normal findings in magnetic resonance imaging in the acute phase, but subsequent cord atrophy.

Assessment of N-glycan heterogeneity of cactus glycoproteins by one-dimensional gel electrophoresis and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry.

Artificial environmental conditions in tissue culture, such as elevated relative humidity and rich nutrient medium, can influence and modify tissue growth and induce spontaneous changes from characteristic organization pattern to unorganized callus. As succulent plants with crassulacean acid metabolism, cacti are particularly susceptible to this altered growth environment. Glycosylated proteins of Mammillaria gracillis tissues cultivated in vitro, separated by SDS-PAGE, were detected with Con A after the transfer of proteins onto the nitrocellulose membrane. The glycan components were further characterized by affinity blotting with different lectins (GNA, DSA, PNA, and RCA(120)). The results revealed significant differences in glycoprotein pattern among the investigated cactus tissues (shoot, callus, hyperhydric regenerant, and tumor). To test whether the N-glycosylation of the same protein can vary in different developmental stages of cactus tissue, the N-glycans were analyzed by MALDI-TOF MS after in-gel deglycosylation of the excised 38-kDa protein band. Paucimannosidic-type N-glycans were detected in oligosaccharide mixtures from shoot and callus, while the hyperhydric regenerant and tumor shared glycans of complex type. The hybrid oligosaccharide structures were found only in tumor tissue. These results indicate that the adaptation of plant cells to artificial environment in tissue culture is reflected in N-glycosylation, and structures of N-linked glycans vary with different developmental stages of Mammillaria gracillis tissues.

Clinical relevance of antibodies against myelin oligodendrocyte glycoprotein in different clinical types of multiple sclerosis.

OBJECTIVE: Myelin oligodendrocyte glycoprotein (MOG) is a highly immunogenic minor component on the outside surface of CNS myelin which is believed to be one of the autoantigens in multiple sclerosis. The aim of this study was to evaluate the diagnostic potential of anti-MOG IgG antibody levels in cerebrospinal fluid (CSF) and serum of patients with relapsing-remitting multiple sclerosis (RRMS), primary progressive multiple sclerosis (PPMS) and non-inflammatory neurological diseases (NIND) as markers for the different clinical types of multiple sclerosis. PATIENTS AND METHODS: Consecutive serum and cerebrospinal fluid samples were taken from 21 patients with RRMS, 7 patients with PPMS and 19 patients with NIND. The antibody responses to MOG were determined in paired samples of these different clinical groups by enzyme-linked immunoassay using a recombinant human MOG protein. RESULTS: The performed analysis indicated that the differences in levels of anti-MOG IgG antibody in serum and cerebrospinal fluid from the patients with RRMS, PPMS or NIND were not statistically significant. CONCLUSION: The assay is not sensitive or specific enough to be used as a differential diagnostic tool for the clinical types of MS, nor for MS itself.

CNS demyelination in autoimmune diseases.

Autoimmune diseases represent a diverse group of disorders that have generally of unknown etiology and poorly understood pathogenesis. They may be organ-specific or systemic, giving rise to overlapping syndromes; more than one autoimmune disease may occur in the same patient. Numerous case reports have documented that multiple sclerosis (MS) may be present concurrently with other autoimmune diseases, most commonly rheumatoid arthritis, autoimmune thyroid disease, type I diabetes mellitus and pernicious anemia. Case reports of disseminated encephalomyelitis (DEM) coincidental with other autoimmune diseases are rare. Many of systemic autoimmune diseases cause central nervous system (CNS) demyelination and are frequently then diagnosed as MS, whereas they often are instances of DEM, the result of vascular, granulomatous or postinfectious manifestations. We have reviewed 15 patients with autoimmune diseases and CNS demyelination in order to determine the nature of the demyelinating process.

Determination of cortical language dominance using functional transcranial Doppler sonography in left-handers.

OBJECTIVE: Verbal analytical functions are primarily related to the left hemisphere in right-handers, but there is yet no agreement about cortical language dominance in left-handers. Also, there are some contradictory reports about sex differences in cortical language lateralization. The aim of this study is to investigate cortical language dominance in left-handers and to explore gender influence on cortical language representation. METHODS: We performed functional transcranial Doppler sonography (previous validated for determination of cerebral language lateralization) during a word generation task, measuring changes in mean cerebral blood flow velocity (BFVmean) in both middle cerebral arteries (MCA) in 150 healthy subjects (75 left-handers and 75 right-handers). In left-handers we observed significant increase BFVmean in right MCA in 58 (77.3%) subjects. Bilateral increase was observed in 11 (14.7%) subjects and increase in left MCA in 6 (8%) subjects. In right-handed group 93.3% subjects showed left cortical dominance, while 6.7% showed bilateral language representation. RESULTS: Current results showed significant (P<0.0001) right hemispheric language dominance in healthy left-handed subjects. CONCLUSIONS: Our results showed significant difference in hemispheric dominance for verbal function between righthanders and lefthanders. Also there is statistically insignificant female gender tendency for bilateral hemispheric language representation in both handedness.

Delay in the diagnosis of multiple sclerosis in Croatia.

BACKGROUND: The National Institute for Health and Clinical Excellence (NICE) guidelines for multiple sclerosis (MS) recommend the time from initial presentation to first neurological evaluation to be no longer than 6 weeks, and a further 6 weeks until any necessary investigations are completed. The aim of this study was to evaluate how many patients with MS are diagnosed within the NICE timelines in two settings specific for Croatia. PATIENTS AND METHODS: All patients with the final diagnosis of clinically isolated syndrome (CIS) or MS in a 6 months period were retrospectively reviewed. We calculated time from first symptom to first neurological evaluation, time from first symptom to MRI scan, time from first neurological evaluation to MRI scan, time from first neurological evaluation to lumbar puncture (LP), time from first symptom to diagnosis and time from first neurological evaluation to diagnosis. We also calculated the percentage of patients fulfilling the NICE timelines. RESULTS: This study showed that only 61.5% of MS patients in Croatia see neurologist within 6 weeks of first symptoms, and 64.1% are diagnosed within next 6 weeks. However, 80% and 100% of patients presented to the emergency room of our hospital (where a visit to a MS clinic can be automatically made) met the NICE guidelines for time from first symptom to first neurological evaluation and time from first neurological evaluation to diagnosis, respectively. CONCLUSION: A specifically designed demyelinating disease diagnostic clinic offers a better service than other existing models in the diagnosis and management of MS patients.

Robustness testing of live attenuated rubella vaccine potency assay using fractional factorial design of experiments.

The potency assay for the freeze-dried live attenuated rubella vaccine is a cell culture based biological assay. The aim of our study was to perform the robustness testing of the rubella vaccine potency assay prior to validation. Seven intra-assay operating conditions that could have an effect on the assay performance were identified and their influence on the overall assay variability investigated by fractional factorial design of experiments (DoE). The robustness testing through DoE showed that the rubella vaccine potency assay is a robust assay. Critical operating conditions can be identified using DoE, which indicates that it is a suitable approach in bioassay robustness studies.

Primary diffuse meningeal melanomatosis.

Primary diffuse meningeal melanomatosis can clinically mimic a wide variety of other conditions, including lymphoma, leukemia, neurosarcoidosis, metastatic carcinoma, acute disseminated encephalomyelitis, subacute meningitis, viral encephalitis, and idiopathic hypertrophic cranial pachymeningitis. We report on a young patient with primary diffuse meningeal melanomatosis who presented with papilledema, flaccid paraparesis, and cognitive impairment. The importance of imaging of the whole central nervous system, cerebrospinal fluid analysis, and pathohistological examination is emphasized in making the appropriate diagnosis.