Whole exome sequencing in Serbian patients with hereditary spastic paraplegia.

Hereditary spastic paraplegia (HSP) is a group of neurodegenerative diseases with a high genetic and clinical heterogeneity. Numerous HSP patients remain genetically undiagnosed despite screening for known genetic causes of HSP. Therefore, identification of novel variants and genes is needed. Our previous study analyzed 74 adult Serbian HSP patients from 65 families using panel of the 13 most common HSP genes in combination with a copy number variation analysis. Conclusive genetic findings were established in 23 patients from 19 families (29%). In the present study, nine patients from nine families previously negative on the HSP gene panel were selected for the whole exome sequencing (WES). Further, 44 newly diagnosed adult HSP patients from 44 families were sent to WES directly, since many studies showed WES may be used as the first step in HSP diagnosis. WES analysis of cohort 1 revealed a likely genetic cause in five (56%) of nine HSP families, including variants in the ETHE1, ZFYVE26, RNF170, CAPN1, and WASHC5 genes. In cohort 2, possible causative variants were found in seven (16%) of 44 patients (later updated to 27% when other diagnosis were excluded), comprising six different genes: SPAST, SPG11, WASCH5, KIF1A, KIF5A, and ABCD1. These results expand the genetic spectrum of HSP patients in Serbia and the region with implications for molecular genetic diagnosis and future causative therapies. Wide HSP panel can be the first step in diagnosis, alongside with the copy number variation (CNV) analysis, while WES should be performed after.

Incidence and mortality rates of Guillain-Barré syndrome in Serbia.

Guillain-Barré syndrome (GBS) is an acute auto-immune polyradiculoneuropathy. A huge variety of GBS incidence and mortality rates has been noted across the world. The objective of the present multi-centric study was to assess the incidence and mortality rates of GBS during a 10-year period in Serbia. We collected data of adult GBS patients who were hospitalized from 2009 to 2018 in all five tertiary healthcare centers in Serbia. The incidence rates per 100 000 inhabitants with 95% confidence intervals (CI) were calculated and further corrected for the estimated number of patients hospitalized in secondary centers. Mortality rates were also assessed. GBS was considered severe if patients were not able to walk at least 10 m without assistance. Six hundred and forty GBS patients were registered in tertiary centers in a 10-year period. The proportion of severe cases was 75% at nadir, and 52% on discharge. GBS incidence rate in Serbia was 1.1 per 100 000 inhabitants, and estimated incidence if patients from secondary centers included 1.2 per 100 000. Peak incidence was observed during the sixth decade of life. During the acute phase, 5.6% of GBS patients died, while overall 9.7% of them died during 6-month period from disease onset. This study contributes to our knowledge about GBS epidemiology. Results will allow us to improve the diagnosis and treatment of GBS patients in Serbia.

Guillain-Barre Syndrome Followed by Covid-19 Infection, Vaccination and Other Precipitating Factors during the Pandemic.

Background and Aims: Guillain-Barré syndrome (GBS) is usually triggered by an infection. Vaccination is mentioned as a possible trigger in a small number of GBS cases. The aim of this study was to notice GBS distinctness provoked by various triggers during the COVID-19 pandemic. Material and Methods: A total of 109 GBS patients were divided into three groups, respectively: COVID-19 infection associated (19 patients), COVID-19 vaccination associated (16 patients) and precipitated by some other factors (74 patients). We compared the clinical, neurophysiological and laboratory characteristics of these three groups. Results: Neither were differences recorded in the age of the patients of these three groups at the time of illness, nor in the number of days from the precipitating factor to the onset of symptoms. There were no clinical differences between groups related to severity of the disease or patients' recovery. The only clinical difference was observed in relation to facial nerve bilateral affection because it was significantly higher in the post-vaccination group. According to neurophysiological findings, demyelinating form dominated in all three groups. Conclusion: Clinical characteristics, electrophysiological findings and laboratory characteristics did not differ significantly in Guillain-Barre syndrome followed by COVID-19 infection, vaccination and other precipitating factors during the pandemic. The bilateral involvement of facial nerves was significantly higher in the post-vaccination group. Most of these cases had a mild form of the disorder-distal paresthesias GBS variant.

Recurrent longitudinally extensive transversal myelitis in a patient with Sjögren's syndrome.

INTRODUCTION: Longitudinally extensive transverse myelitis (LETM) is a transversal myelitis that extends through three or more vertebral segments in length. CASE REPORT: A 52-year-old woman was hospitalized due to pain in the lumbar region, difficulty in walking, hypoesthesia of the anogenital area and urinary retention. In the past medical history, two years earlier, the patient had been diagnosed with transversal myelitis confirmed by MRI of the cervical spine and six months earlier, the patient was diagnosed with primary Sjögren's syndrome (SS). During the current hospitalization MRM of the spinal cord revealed extensive inflammatory lesions of almost the whole spinal cord. Lumbar puncture (LP) revealed mild pleocytosis and slightly increased protein level. Isoelectric focusing of cerebrospinal fluid (CSF) and serum proteins was normal. Visual evoked potentials were normal. Serological testing excluded acute viral infections. Corticosteroid therapy was applied with good therapeutic response. Control MRI revealed regression of pathological changes in the spinal cord. CONCLUSION: A wide range of disorders can cause LETM, but usually the first line diagnosis is neuromyelitis optica (NMO). Based on the detection of NMO immunoglobulin G in the serum of affected patients, a variety of allied disorders were grouped under the name of NMO spectrum disorders, including recurrent myelitis associated with LETM and myelitis associated with autoimmune disorders such as SS. There have been only a few cases reported in the literature with recurrent LETM associated with non-organ specific autoimmune disorder.

[Contemporary treatment neuropathic pain].

INTRODUCTION: Neuropathic pain, or pain associated with disease or injury to the peripheral or central nervous system, is a common symptom of a heterogeneous group of conditions, including diabetic neuropathy; trigeminal neuralgia, postherpetic neuralgia and spinal cord injury. Chronic neuropathic pain should not be thought of as a symptom. It should truly be thought of as a disease with a very complicated pathophysiology. PATHOPHYSIOLOGY: The mechanisms involved in neuropathic pain are complex and involve both peripheral and central pathophysiologic phenomenon. The underlying dysfunction may involve deafferentation within the peripheral nervous system (e.g. neuropathy), deafferentation within the central nervous system (e.g. post-thalamic stroke) or an imbalance between the two (e.g. phantom limb pain). CLINICAL CHARACTERISTICS: Neuropathic pain is non-nociceptive, in contrast to acute nociceptive pain, and it can be described as "burning", "electric", "tingling", and "shooting" in nature. TREATMENT: Rational polypharmacy is often necessary and actually it is almost always the rule. It would be an exception if a patient was completely satisfied with his treatment. Treatment goals should include understanding that our patients may need to be titrated and managed with more than one agent and one type of treatment. There should be the balance of safety, efficacy, and tolerability. CONCLUSION: There are many new agents and new applications of the existing agents being currently studied which will most certainly lead to even more improved ways of managing this very complicated set of disorders.

The sensitivity of electromyoneurography in the diagnosis of diabetic polyneuropathy.

Diabetic polyneuropathy is a complex set of clinical syndromes, which deplete various regions of the nervous system. The process leading to diabetic neuropathy is multi-factorial. Its symptoms are paresthesia, dysesthesia and pain. The signs of damage to the peripheral neurons are hypoesthesia, hypoalgesia, hyperesthesia and hyperalgesia, decreased tendon reflexes, and, possibly, weakness and muscle atrophy. There is no universal classification. Electromyoneurography is indispensable in the diagnosis of diabetic polyneuropathy. However, there is no agreement on the most sensitive parameter for an early diagnosis. One hundred patients with diabetes mellitus were examined in order to investigate the sensitivity of different electromyographic parameters. Electromyographic techniques proved to be entirely sensitive for the early diagnosis of diabetic polyneuropathy. Some of the parameters are more suitable for an early detection of peripheral nerve damage, and others, which are not so sensitive but easy to use and stable, are suitable to follow up the course of diabetic polyneuropathy.

Quality of life research in patients suffering from tension type headache.

The tension type headache is the most common headache type, which many men and women suffer from in one period of their life and aggravates business productivity, family and social functioning. Quality of life estimation in patients suffering from tension type headache enables us to get a better insight into the impact of the disease on the patient. The comparison among the quality of life in the patients suffering from tension type headache and the quality of life in the control group subjects has been carried out in a research by applying the QVM questionnaire. The obtained results have shown a significant difference in the quality of life and its sub domains indicating worse quality in the patients suffering from tension type headache.

[Menstrual migraine].

INTRODUCTION: The prevalence of migraine in childhood and adolescence has not changed to a great extent, but it increases in adolescence, especially in female adolescents. MENSTRUAL MIGRAINE--DEFINITION: There are two types of menstrual migraine: true menstrual migraine and menstrually related migraine. True menstrual migraine occurs predominantly around menstruation, whereas menstrually related migraine occurs during menstruation, but also at other times during the month. CAUSES: Exaggerated or abnormal neurotransmitter responses to normal cyclic changes in the ovarian hormones are probably the basic cause of menstrual migraines. The fall in estrogen levels during menstrual cycle is trigger for the menstrual migraine. SYMPTOMS: Menstrual migraine has the same symptoms as other types of migraine, but the pain is stronger, it lasts longer, and it is more frequent than other types of migraines. DIAGNOSIS: In order to make a diagnosis, women are asked to keep a headache diary for three months. If the migraine headache is severe and occurs regularly between two days before and three days after the start of menstrual bleeding, it is true menstrual migraine. THERAPY: Menstrual migraines are more difficult to treat than other types of migraines. Treatment principles for menstrual migraine are the same as for migraines in general, with certain particularities. CONCLUSION: Hormonally associated migraine is a specific clinical entity. It is important to diagnose the type of migraine, considering the fact that a decline in estrogen level at the end of menstrual cycle triggers migraine, so it can be treated by low levels of estrogen.

[Multiple brain abscesses: a case report]. / Prikaz slucaja multiplih apscesa mozga.

CASE REPORT: 10 days before admission a 45-year old female experienced general weakness, and T 38 degrees C. During that period she had no cardio-respiratory nor neurological complaints, and the temperature varied between 37.5 degrees C and 38 degrees C. Her medical history was unremarkable, without immunodeficiency. The day before admission she presented with left arm paresis and during the next day it progressed to paralysis. She had no headache. On admission the following diagnostic procedures were performed: the cranial CT scan showed two lesions (possibly meta lesions). Chest X-ray was normal. WBC=15x10(9)/L, ESR=90/120. On the second day following admission brain MRI showed multiple abscesses in both hemispheres, mostly in the gray/white junction. High doses of IV metronidasol, cephtriaxon and cipfloxacin were administered without obtaining specimens for micro-biological diagnosis. In next two days she developed coma, respiratory insufficiency and septic temperature. Brain surgery was not performed due to severe involvement of the brain with multiple abscesses. Repeated chest X-ray revealed bilateral pneumonia. A lethal outcome occurred on the third day, regardless of all efforts. Autopsy showed multiple brain abscesses as well as on the lungs and liver. A beta-hemolytic streptococcal infection was established. CONCLUSIONS: Prevention includes treatment of the infection source. The classic triad of headache, fever and focal deficit occur in less than 50% of patients. Even in such cases brain abscess must be reconsidered CT appearance of brain abscess is similar to that of neoplastic and other infectious and non infectious diseases--especially in the stage of early cerebritis. If the CT findings are not clear, MRI should be performed.