Ervina Bilić

High frequency of cutaneous manifestations including vitiligo and alopecia areata in a prospective cohort of patients with chronic graft-vs-host disease.

Aim To determine the frequency and the characteristics of cutaneous manifestations, especially vitiligo and alopecia areata, in patients with chronic graft-vs-host disease (cGVHD). Methods 50 patients with cGVHD were prospectively enrolled in the observational study protocol and evaluated by an experienced dermatologist. The evaluation was focused on the clinical spectrum of skin and adnexal involvement, and the cutaneous GVHD score was determined according to National Institutes of Health (NIH) Consensus criteria. The presence of vitiligo, alopecia, xerosis, nail changes, and dyspigmentation was also assessed. Results Out of 50 cGVHD patients, 28 (56%) had skin involvement, and 27 of them (96%) had hypo and/or hyperpigmentations. 11 patients (39%) had a mild cutaneous NIH cGVHD score, 22% moderate, and 39% severe. 15 (30%) patients had nail changes and 10 (20%) had vitiligo or alopecia areata. Univariate analysis showed that patients with vitiligo/alopecia areata received more lines of prior systemic immunosuppressive therapy (P = 0.043), had lower Karnofsky performance status (P = 0.028), and had a higher B-cell number (P = 0.005), platelet count (P = 0.022), and total protein (P = 0.024). Vitiligo and alopecia areata were associated with higher NIH skin score (P = 0.001), higher intensity of immunosuppressive treatment (P = 0.020), and total body irradiation conditioning (P = 0.040). Multivariate regression model showed that patients with higher NIH skin scoring were 3.67 times more likely to have alopecia and/or vitiligo (odds ratio 3.67; 95% confidence interval 1.26-10.73), controlled for all other factors in the model (age at study entry, number of B-cells, platelet count, and global NIH score). Conclusion These data indicate that vitiligo and alopecia areata occur more frequently in cGVHD than previously reported.

High prevalence of small- and large-fiber neuropathy in a prospective cohort of patients with moderate to severe chronic GvHD

High prevalence of small- and large-fiber neuropathy in a prospective cohort of patients with moderate to severe chronic GvHD

Stiff-person syndrome in a female patient with type 1 diabetes, dermatitis herpetiformis, celiac disease, microcytic anemia and copper deficiency Just a coincidence or an additional shared pathophysiological mechanism?

The low level of serum copper in presented patient with Stiff-person syndrome, type 1 diabetes, dermatitis herpetiformis, celiac disease and microcytic anemia opens a question of the role of copper and possibly other trace elements in the development of autoimmune diseases.

Postural orthostatic tachycardia syndrome (POTS) as presenting symptom of CIDP

An 18-year-old-male presented with a history of transient losses of consciousness (TLOC). His initial symptoms were light-headedness, dizziness, weakness, palpitations and blurring of vision, which occurred on standing from a supine position or during physical exertion. He went on to develop four episodes of TLOC in period of 2 years prior to presentation. At the same time he noticed tremor in his upper extremities, mostly during activity. Loss of consciousness occurred while walking or climbing stairs and was followed by a period of anterograde and retrograde amnesia that lasted up to 30 min. In these 30 min the patient did not know his name, his parents’ names, where he lived or any other data from his past. However, after this period he knew every detail during these 30 min of amnesia. Based on this we considered these symptoms psychogenic. His family history was negative for neurological disorders. On presentation a bilateral rhythmic tremor was noted during posture on all four limbs. The tremor was not provoked by the upright position, but was also present when the patient was in bed at rest when he would outstretch his arms. The rest of the neurological examination was normal, muscle strength on all four limbs was 5/5, reflexes were 1?, there was no sensory loss. MRI of the brain and EEG were normal. Prolonged head-up tilt table test (HUTT) revealed postural orthostatic tachycardia syndrome (POTS) (Fig. 1). Levels of norepinephrine in tilted position were\3.5 nmol/L (1.2 nmol/L in the supine and 2.6 nmol/L in the tilted position; ref. range \2.49), indicating neuropathic variant of POTS. There were no clinical signs of dehydration; the blood urea nitrogen, creatinine and 24-urine sodium were within normal limits. The evaluation of cardiovascular autonomic function [heart rate variability with deep respiration, the heart rate and blood pressure response to a Valsalva maneuver, heart rate response to postural change (30:15 ratio)] was normal. Electromyoneurography (EMNG) showed demyelinating sensorimotor polyneuropathy with fulfilled electrodiagnostic criteria for CIDP, according to EFNS guidelines (namely: the conduction block was found in four peripheral nerves with increased CMAP duration, the distal motor latencies were prolonged in six nerves and prolongation of F-wave latencies was found in three nerves) (Table 1) [1]. Laboratory tests including complete blood count, serum iron concentration, fasting blood glucose, HbA1C, vitamin B12, folic acid, paraneoplastic antibodies (Hu, Yo, Ri), Borrelia and syphilis serology, serology for viruses (HBV, HCV, HIV, CMV, EBV) and thyroid function tests were normal. Anti-nuclear antibodies, extractable nuclear antigen profile, antineutrophil cytoplasmic antibodies, anticardiolipin IgG and IgM antibodies, C3, C4, CH50, antithyroid peroxidase antibodies, anti-streptolysine titer, rheumatoid factor were negative. Serum and urine paraprotein detection by immunofixation was negative. CSF & Mario Habek mhabek@mef.hr

How Croatian patients suffering from amyotrophic lateral sclerosis have been turned into medical tourists – a comment on a medical and social phenomenon

In the last few weeks, Croatia has witnessed a rarely seen surge of public interest in neurologic disease amyotrophic lateral sclerosis (ALS). In a rather organized manner and with significant media support, money was raised to send Croatian patients suffering from ALS to China to receive a treatment referred to as “stem cell therapy.” Even before this action, individual Croatian patients, including children suffering from a variety of diseases, tried on their own to seek this type of “therapy.” What makes the current situation specific is that a subgroup of patients offered to another group of patients a financially covered “package” for a treatment in a hospital in China without consulting their doctors or other Croatian medical experts. Upon returning home, the patients, together with their doctors and families, are now facing consequences of this medical and social phenomenon.

Epileptic seizure as initial and only manifestation of neuroborreliosis: case report

Lyme borreliosis is a multisystem disease caused by the spirochete Borrelia burgdorferi [1]. Neuroborreliosis may be manifested as Bannwarth’s syndrome (symptom triad: facial palsy, lymphocytic meningitis, and radicular pain), progressive encephalomyelitis, encephalopathy, cerebral vasculitis, transverse myelitis, amyotrophic lateral sclerosis syndrome, internal hydrocephalus, dementia, depression, axonal motor polyneuropathy, acrodermatitis chronica atrophicans, radicular lesions, and sensory neuropathies [1]. We present a patient who developed epileptic seizure as initial and only manifestation of neuroborreliosis.

The Project MinE databrowser: bringing large-scale whole-genome sequencing in ALS to researchers and the public.

Amyotrophic lateral sclerosis (ALS) is a rapidly progressive fatal neurodegenerative disease affecting 1 in 350 people. The aim of Project MinE is to elucidate the pathophysiology of ALS through whole-genome sequencing at least 15,000 ALS patients and 7,500 controls at 30X coverage. Here, we present the Project MinE data browser (databrowser.projectmine.com), a unique and intuitive one-stop, open-access server that provides detailed information on genetic variation analyzed in a new and still growing set of 4,366 ALS cases and 1,832 matched controls. Through its visual components and interactive design, the browser specifically aims to be a resource to those without a biostatistics background and allow clinicians and preclinical researchers to integrate Project MinE data into their own research. The browser allows users to query a transcript and immediately access a unique combination of detailed (meta)data, annotations and association statistics that would otherwise require analytic expertise and visits to scattered resources.

Epilepsy caused by superficial hemosiderosis of the central nervous system

Dear Editor-in-Chief, Superficial hemosiderosis of the central nervous system (CNS) is an uncommon and often unrecognized disorder caused by small repeated hemorrhages into the subarachnoid space, resulting in CNS hemosiderin deposition in the subpial layers. The etiology is reported to be idiopathic in 35% of cases, CNS tumor in 15%, trauma in 13%, and arteriovenous malformation in 9% of cases. It is rarely caused by intradural neurosurgical operations, nerve root avulsion, or other causes of subarachnoid hemorrhage [1]. Xanthochromia is a common finding. Also, magnetic resonance imaging (MRI) of the CNS reveals a rim of hypointensity on T2-weighted images involving the surface of the brainstem, cerebellum, and cortical fissures. The classical symptoms include sensorineural hearing impairment, visual impairment, slowly progressing cerebellar ataxia, and pyramidal signs, but this syndrome rarely clinically presents with seizures. To date, there are only few reported cases of seizures caused by superficial siderosis [1–3]. A 70-year-old retired senior medical nurse has presented with a sensorineural hearing loss in the last 10 years, slowly progressing gait ataxia, hyposmia, spastic paraparesis, urinary incontinence, and epilepsy—occipital lobe seizures with visual hallucinations, forced blinking, and contralateral eye deviation, followed by impaired awareness, which pointed to the propagation of epileptogenesis into the temporal lobe, and with secondary generalization (confirmed with video-EEG monitoring) (Fig. 1). Seizures started at the age of 69. In her history, she had hypertension, hyperlipidemia, and cerebellar stroke at the age of 45, as well as head contusion and brain concussion in a traffic accident at the age of 46. Gait ataxia was initially connected to cerebellar stroke, but due to progressive course, we have searched for other causes. MRI provided the etiologic diagnosis based on typical low-density signals from the brain, brainstem, cerebellar, and spinal cord surfaces on T2 and gradientecho-weighted sequences (T2*)—hemosiderosis as a consequence of a previous subarachnoid hemorrhage (Fig. 2). Cerebrospinal fluid (CSF) analysis revealed xanthocromia. Multislice CT angiography of the head and neck blood vessels and well as spinal cord digital * Zeljka Petelin Gadze zpetelin@mef.hr

Neurosyphilis: The shape of a rising threat

This report describes a case of neurosyphilis presenting with memory disturbances, attention deficit, and acute psychotic decompensation in an immunocompetent man. Despite the known connection of neurosyphilis with psychiatric symptoms, this cause often remains unrecognized. This report emphasizes the importance of maintaining a suspicion for the disease in patients with vague symptoms and describes the diagnostic difficulties.

Carpal Tunnel Syndrome

Carpal tunnel syndrome (CTS) is a compressive focal neuropathy of the median nerve (NM) at the wrist. We hypothesize that reverse Phalen’s test rather than the previously commonly proposed classic Phalen’s maneuver was a logical maneuver in the diagnosis of CTS from the anatomic, pathophysiological and electrophysiological viewpoint. Dorsal flexion of the hand results in an increase in the flexor retinaculum tension (RFT), extension of the finger long flexor muscle tendons and consequential NM entrapment between the tendons and flexor retinaculum (RF). Thus, the carpal tunnel (CT) volume is reduced, the intra-tunnel pressure is increased, while the RF to NM distance is decreased. On Phalen’s maneuver, the forced palmar hand flexion entails opposite consequences i.e. reduced RFT, relaxation of the finger long flexor muscle tendons, decreased pressure upon NM, slight increase in the CT volume, decreased intra-tunnel pressure and increased RF to NM distance. The hypothesis can be tested by a conductive NM study, preferably at three positions: mid-position (palmar/volar angle 180 degrees); forced dorsal flexion (palmar/volar angle about 270 degrees); and forced palmar (volar) flexion (palmar/volar angle about 90 degrees). Relative to mid-position, “deterioration” of electroneurography (ENG) finding is observed in dorsal flexion, whereas “improvement” of ENG finding is recorded in palmar flexion.