Dimitrios Parissis

Meningioma growth and interferon beta-1b treated multiple sclerosis: coincidence or relationship?

Although the coincidence of multiple sclerosis (MS) and central nervous system (CNS) tumors has been reported in over 30 cases in English literature, meningioma growth was associated with interferon-beta (INF-b) treated MS only in two of them. We report the case of a 19-year-old woman with clinically possible, laboratory supported MS, and a concomitant right intraventricular tumor with magnetic resonance imaging (MRI) characteristics consistent with meningioma (similar signal with grey matter on T1 and T2-weighted images and homogenous, intense enhancement). Two years after initiation of INF-b treatment, follow-up brain MRI revealed enlargement of the intraventricular mass and relative increase in the number of white matter lesions without significant clinical deterioration. She underwent almost total resection of the mass and histology confirmed the diagnosis of papillary meningioma. Based on the immunohistochemistry results, we speculate that INF-b resulted in meningioma growth by enhancing platelet derived growth factor (PDGF) receptors or/and down-regulating transforming growth factor receptors on the tumor itself.

Inclusion body myositis in a patient with a presumed diagnosis of post-polio syndrome

Sirs: Sporadic inclusion body myositis (IBM) is a distinctive form of inflammatory myopathy and an important cause of progressive muscle wasting and weakness in later life [7]. Post-polio syndrome is defined as “the development of new muscle weakness and fatigue in skeletal or bulbar muscles, unrelated to any known medical cause, that begins 25–30 years after an acute attack of paralytic poliomyelitis” [4]. Searching the literature we found only two cases of pathologically confirmed inclusion body myositis in patients with a known history of paralytic poliomyelitis [1, 9]. In this letter we describe a similar case and discuss the data, which can lead to the reliable differential diagnosis between inclusion body myositis and postpoliomyelitis muscular atrophy. A farmer, aged 61 years, was referred to our department because of painless muscular weakness in his lower legs and right arm; his left arm had been severely paretic and atrophic since the age of 3 years following an acute attack of paralytic poliomyelitis. The new symptoms had started six months ago and there was progressive disability. At the time of the referral the patient could not rise from a chair and climb stairs without support. Neurological examination revealed muscular weakness mainly localized in the quadriceps femoris muscles (Medical Research Council Grade 2) and tibialis anterior in the lower limbs bilaterally, as well as in the deltoid, biceps brachii and deep finger flexor in the right arm (MRC Grade 3). Muscle tone and tendon reflexes were diffusely depressed. Severe atrophy was obvious in the quadriceps femoris. Sensory examination proved normal and the Babinski sign was not elicited. Routine laboratory tests showed mild elevation of creatine kinase (CK). The immunological profile of the patient was not normal; there were polyclonal hyperglobulinemia, positive titer of antinuclear antibodies (ANA) and low values of C4 complement indicating an autoimmune disorder. However, after an extensive review of the laboratory tests, the patient did not meet the criteria of any autoimmune disease. Needle electromyography of proximal (e. g. deltoid, vastus medialis) and distal muscles (tibialis anterior) of the right upper and the lower limbs revealed abnormal spontaneous activity, consisting of numerous fibrillation potentials and trains of positive sharp waves; additionally there was an excess of small amplitude and short duration polyphasic motor unit action potentials. Recruitment pattern was full with low amplitude potentials, indicating some kind of myopathic disorder. The electrophysiological findings in the left upper limb were compatible with a longstanding neurogenic disorder. An open muscle biopsy was performed on the right quadriceps (vastus medialis) muscle. In multiple frozen as well as paraffin sections of the skeletal muscle, a dense inflammatory infiltration and fibrosis of the endomysium was profound (Fig. 1). The inflammatory cells were mainly lymphocytes and most of them were T cells (Fig. 2). A variation of fiber size with large and small rounded fibers as well as degenerated fibers with or without phagocytosis was frequent. Other myopathic features, such as internal nuclei, splitting or ring fibers were also found. In some of the larger ones, phagocytosis without necrosis was obvious (Fig. 3). In a small number of muscle fibers one or more vacuoles with granular material were easily recognizable. This granular material was stained red by trichrome Gomori (Fig. 4). There were no signs of denervation or reinnervation. The morphology of this muscle biopsy specimen was consistent with inclusion body myositis. Unfortunately, an electron microscopic study of the muscle specimen was not performed. Treatment with prednisolone per os (0,75 mg/kg/day) was started tapering to a low maintenance dose after a period of 3 to 6 weeks combined with azathioprine 150 mg daily. In the follow-up after 3 months the assesment of muscle function in selected upper and lower limb muscle groups showed no further deterioration of the muscle strength. We believe that our patient suffered from inclusion body myositis and not from post-poliomyelitis muscle atrophy (PPMA) as originally was thought. At first, the selective pattern of muscle involvement in both the upper and lower limbs and especially the finding of knee extensor weakness that exceeded hip flexor weakness as well as finger flexor weakness were highly suggestive of inclusion body myositis. Our patient had also a progression of his symptoms noticeable in months, which is not consistent with the extremely slow course of PPMA. Moreover, new post-polio symptoms appear to begin after a mean period of approximately 30 years (range, 15 to 55) after the original attack of acute LETTER TO THE EDITORS

Chromosome 22q11.2 deletion syndrome: an underestimated cause of neuropsychiatric impairment in adolescence

Sirs: Chromosome 22q11.2 deletion syndrome is a common multiple malformation syndrome estimated to affect between 1 in 4000 and 1 in 5000 individuals [1]. With the advent of molecular genetics a 3-Mb microdeletion within 22q11 was found to underlie a heterogeneous group of disorders with overlapping features, such as Di George and velocardiofacial syndrome [2, 3]. The phenotype of the disorder has expanded considerably within the last few years, whereas the clinical features vary significantly among affected individuals [4]. However, cardiovascular defects, immunological deficits, neurodevelopmental retardation, craniofacial abnormalities and hypocalcemia are recognised as the major and most frequent manifestations of the syndrome [5]. A 17-year-old boy presented with a gradual cognitive and behavioral decline over the last 18 months. The symptom onset coincided with a febrile gastrointestinal tract infection and was initially characterized by anxiety, altered sleep pattern, bizarre statements and actions and lack of initiative. The patient exhibited bland, and at times inappropriate affect, whereas his thought and behavior were mildly but progressively disorganised. The patient became eventually socially withdrawn and was unable to attend to his school activities. However, no hallucinations or delusions were present. He showed poor response to neuroleptic medication and remained withdrawn with psychomotor retardation and poverty of speech. His past medical history was significant for non-febrile neonatal seizures, which were attributed to hypocalcemia. At that time, he was diagnosed as having hypoparathyroidism, whereas further investigation showed thymic hypoplasia with marginally reduced T-cell numbers. However, no chromosomal abnormality was found on karyotyping. Developmental milestones were also delayed; he began to walk at 17 months and first combined single words into full sentences around 48 months of age. The patient had attended regular school classes, but his overall school performance had always been poor with prominent deficits in visuo-spatial abilities and executive functioning. He was also diagnosed as having bilateral stenosis of the external auditory canal, and an inguinal hernia had been repaired at 3 months of age. Moreover, the patient had an episode of septicemia due to pneumococcal infection at the age of 13. His family history was unremarkable, apart from a diagnosis of schizophrenia in a paternal great uncle. The patient was admitted and evaluated mainly by the neurology services. On examination, he was noted to have slightly dysmorphic facial features consisting of broad nasal root, malar flattening and relative retrognathia. His speech was hypernasal without overt cleft palate, but the general neurological and physical examination were otherwise unremarkable. Neuropsychological assessment revealed moderate deficits on verbal, as well as non-verbal reasoning tests, whereas the patient’s visual perceptual skills and memory appeared to be mildly impaired. The prominent difficulty of the patient in sustaining concentration exaggerated his deficits, but his overall neuropsychological profile was consistent with significant cerebral dysfunction. Routine hematology showed mild thrombocytopenia, increased free thyroxin values and marginally decreased calcium levels. Routine EEGs revealed on one occasion brief bursts of generalised epileptiform activity; however, successive EEGs as well as video-EEG monitoring failed to detect any abnormality. MRI of the brain using volumetric acquisition as well as echocardiogram proved normal. The patient was then extensively investigated in a tertiary university centre in order to exclude an underlying neurological disorder. Blood films for acanthocytes, serum copper and ceruloplasmin, slit lamp examination, antibasalganglia antibodies, white cell enzymes as well as very long chain fatty acids, plasma amino acids and urine organic acids were either normal or negative. The suspicious EEG findings led to skin biopsy for Lafora disease, which revealed no abnormality. Subsequently, a muscle biopsy was undertaken which provided no evidence for a mitochondrial encephalomyopathy. Finally, on readmission 2 years later a fluorescence in-situ hybridization (FISH) using the N25 probe was performed, which demonstrated a microdeletion within chromosome 22q11.2. It is well established that individuals with chromosome 22q11.2 deletion syndrome are at risk to develop a range of psychiatric illnesses. Early reports cite a high prevalence of psychotic disorders, specifically schizophrenia, among adults carrying the deletion and LETTER TO THE EDITORS

Inflammatory aneurysm of the abdominal aorta in a patient treated with ropinirole

Retroperitoneal fibrosis, inflammatory aneurysm of the abdominal aorta and perianeurysmal retroperitoneal fibrosis are three closely related entities that belong to the spectrum of chronic periaortitis [1]. Retroperitoneal and pleuropulmonary fibrosis are well known but rare complications of the treatment with ergolinic dopamine agonists of Parkinson’s disease [2, 3]. To our knowledge, ropinirole, a non-ergot derived dopamine agonist, has never been associated with fibrotic complications localized to the retroperitoneal space. A 72-year-old man was admitted to our clinic because of a febrile illness with significant anorexia and fatigue. At presentation, he suffered from moderately advanced Parkinson’s disease, which was diagnosed 11 years ago. His treatment consisted of levodopa/carbidopa and ropinirole throughout his disease course. At the time of admission he was on 1.35 g/day of levodopa and 15 mg/day of ropinirole. On admission, apart from a fever of 38.5 C and the parkinsonian signs, his physical examination was unremarkable. Routine laboratory tests showed moderate normochromic-normocytic anemia (hemoglobin 8.9 g%), elevation of C-reactive protein level (14 mg%), elevated erythrocyte sedimentation rate (124 mm/ h), ferritin (1381 ng/ml) and fibrinogen (7.9 g/l). Further investigation revealed mild increase of serum IgA (510 mg/dl), beta2 microglobulin (4.03 mg/l) and total globulin level (3.7 g/dl). Extensive serological studies for autoimmune and infectious disorders were either normal or negative, whereas bone marrow aspirate and biopsy findings were compatible with reactive changes secondary to chronic inflammation. Both chest X-ray and chest CT scans showed no abnormalities. CT imaging of the abdomen revealed findings indicative of periaortic edema and inflammatory soft tissue formation without aneurysm (Fig. 1). Ropinirole withdrawal was suggested, but the patient declined. Administration of i.v. methylprednisolone at 80 mg/day resulted in complete relief of symptoms within a few days, and acute phase reactants started to decline. Similarly, anemia gradually responded to steroid therapy. The patient remained in clinical remission during steroid tapering to a maintenance dose of 10 mg/day. However, a follow-up CT examination performed 3 months later demonstrated a 4 cm saccular aneurysm arising from the right anterolateral portion of the aorta (Fig. 2). In this report we present a patient who developed inflammatory aneurysm of the abdominal aorta while on long-term treatment with ropinirole. In this disorder fibroinflammatory tissue develops around a dilated aorta, but does not cause obstructions of the adjacent structures. Inflammatory aneurysm of the abdominal aorta together with retroperitoneal fibrosis and perianeurysmal retroperitoneal fibrosis are believed to have a common autoimmune pathogenesis and share many clinical, laboratory and histological features [4]. D. Parissis (&) B’ Department of Neurology, Aristotle University of Thessaloniki, AHEPA Hospital, 1, Stilponos Kyriakidi Str, 546 36 Thessaloniki, Greece e-mail: dparissis@gmail.com

Levetiracetam as alternative treatment in Jeavons syndrome.

We report on a 25 year old female patient who had a diagnosis of Jeavons syndrome since her childhood. Although valproate led to seizure freedom, she developed persistent reproductive endocrine disorders attributed to this drug. The withdrawal of valproate in parallel with an initiation of levetiracetam monotherapy resulted in a maintenance of clinical remission and a resolution of these abnormalities. This case together with relevant literature data supports the view that the use of levetiracetam might be of benefit for female patients with Jeavons syndrome.

Intrathecal Gadolinium for Magnetic Resonance Myelography in Spontaneous Intracranial Hypotension: Valuable But May Be Risky

tion as outlined in the National Comprehensive Cancer Network guidelines. However, in the event that this resection is not possible, radiotherapy and postradiation chemotherapy are recommended. The professional opinion of the neurosurgeons treating the patient presented in the article1 was that surgical resection for the ill-defined lesion would be difficult and could result in neurologic sequelae that would be unacceptable for the patient. After that decision was made, the clinical course of action was radiotherapy followed by chemotherapy and close follow-up. We were not involved in the clinical decision making for this patient’s case. About 2 years after diagnosis, serial monitoring by magnetic resonance imaging discovered a more discrete enhancing nodule near the initial biopsy site. This nodule was completely resected and the patient is doing well. We also agree that cerebellar mutism is mainly seen in pediatric cases with surgical resection of posterior fossa tumors. This article1 was not meant to review the characteristics of cerebellar mutism. The main concern was extension of the tumor into the brainstem that could have caused more serious consequences.

Isolated IgG4-related hypertrophic pachymeningitis.

Hypertrophic pachymeningitis represents a rare neurological disorder with variable symptoms such as headache, cranial nerve palsies, motor weakness and seizures due to meningeal inflammation and dural thickening. These clinical manifestations are mainly due to vessel and nerve compression. We report a rare case of isolated IgG4-related pachymeningitis showing characteristic histopathological findings.

Can 'football-team color-code' compensate for anomia? : The case study of FN, a patient with color anomia

A case study is reported on large ischemic infracts involving cortical and subcortical areas of the parietal lobes bilaterally, especially left temporo-parietal and right parietal. On examination, the diagnosis of vascular dementia with color anomia, optic aphasia for colors, was established. The patient (FN) showed great difficulty in understanding a scene as a whole and in describing complex scenes. FN’s oral comprehension skills at word and sentence level were satisfactory and he exhibited communicative effectiveness during conversation. He could read letter by letter, but could not make simple judgments of shapes. FN exhibited a marked inability to name colors presented to him visually and to indicate or point to the color requested from the examiner. The most interesting of all the patient’s characteristics was the strategy – a football-team color-code – he had developed for compensating for his inability to name colors.

Estimating Everyday Neuropsychological Functioning in Multiple Sclerosis: Reliability and Validity of the Greek Multiple Sclerosis Neuropsychological Questionnaire

The Multiple Sclerosis Neuropsychological Questionnaire is a brief screening questionnaire for the assessment of everyday neuropsychological competence of patients with Multiple Sclerosis. The aim of the present study was to examine psychometric properties of the Greek version of the instrument. One hundred and three MS patients and 60 informants participated in the present study and completed the questionnaire. From the initial patient sample, 51 participants completed broadly used neuropsychological tests and measures estimating cognitive failures and depression. Moreover, after a six-month interval the MSNQ was administered to 58 patients from the initial sample in order to explore test-retest reliability. Cronbachs α was 0.92 and 0.93 for patient and informant forms, respectively. The patient form was correlated significantly with measures of cognitive failures and depression. Low correlations were found between the informant form and performance on cognitive tests. In regard to the patient form, significant correlation was observed between repeated administrations and, psychometrically, the three-factor structure was preferable than the one-factor structure. The present study confirms the already established pattern of correlations among the two MSNQ forms, neuropsychological test performance and depression measurements. Additional research is needed in order to define a cut-off score for the MSNQ-I providing further information about the diagnostic interpretability of the instrument.

Neuromyotonia Confined to Faciobulbar Muscles in a Patient with Myasthenia Gravis

Acquired neuromyotonia (NMT) is a part of the spectrum of peripheral nerve hyperexcitability (PNH) syndrome, characterized by spontaneous and continuous muscle fiber activity, cramps and stiffness of peripheral nerve origin. We report the interesting case of a patient with myasthenia gravis (MG), who developed isolated facial and lingual NMT. A 72-year-old man developed non-progressive dysphagia and dysphonia over a period of 2 months. He described a feeling of tightening of his tongue and throat that interfered with swallowing and speech. He denied weakness or stiffness of facial and limb muscles apart from frequent calf cramps. Past medical history included arterial hypertension and wellcontrolled, acetylcholine receptor antibody seropositive MG since 2013 manifested by episodic diplopia and ptosis. There was no history of insomnia, excessive sweating, sensory symptoms or CNS disease. Neurological examination demonstrated prominent undulating rippling of orbicularis oris and continuous, irregular twitching of the tongue (see accompanying Video 1). There was no evidence either of tongue atrophy or involuntary palate movement. Limb and facial muscle strength was normal and there were no abnormalities on ocular, deep tendon reflexes and sensory testing. EMG sampling of the genioglossus and right orbicularis oris revealed sustained neuromyotonic discharges (see Fig. 1), whereas occasional fasciculations were recorded from the right tibialis anterior and upper portion of the trapezius muscle. Motor and sensory nerve conduction studies, as well as repetitive stimulation of the right facial nerve proved within normal limits. Further investigations including MRI of the brain and base of the scull disclosed no abnormalities. Serological studies for antibodies against muscle-specific kinase (MuSK), voltage-gated potassium channel (VGKC), and contactin-associated protein 2 (Caspr2) were similarly negative. Finally, CT scan of the thorax, abdomen and serum tumor markers did not demonstrate evidence of thymoma or other malignancy. The patient was treated with prednisolone 1 mg/kg/alternate days without clinical response. Subsequently, symptomatic treatment with carbamazepine 600 mg/day was initiated leading to sustained clinical benefit during an 18-month follow-up period. It is well established that MG, among other autoimmune, axonopathic and paraneoplastic disorders, may be associated with NMT. In our patient, we detected neuromyotonic discharges defined by their extreme frequency (>120 Hz) and the decrementing pattern of the amplitude of the motor unit action potentials within the burst. In this context, our patient’s symptoms might be attributed to oropharyngeal muscle stiffness. Alternatively, neuromuscular transmission failure resulting from continuous high rates of motor units firing could theoretically be implicated, although single-fiber EMG recordings are normal in patients with NMT. Simon et al. described two MG patients positive for MuSK antibodies who developed PNH. Interestingly, their first patient developed facial NMT similar to our case. The authors hypothesized that these antibodies might have induced a relative deficiency of acetylcholinesterase (AChE) activity by disrupting MuSK-AChE binding, resulting in increased synaptic ACh concentration. Accumulation of ACh could potentially initiate ectopic nerve discharges by modifying the balance of presynaptic nicotinic and muscarinic channel activation. In our patient, NMT was confined to cranial muscles. Of note, isolated bulbar myokymia or NMT is a well-described complication following head and neck radiotherapy for nasopharyngeal carcinoma. Other acquired disorders that have been traditionally associated with faciobulbar NMT include multiple sclerosis, pontine tumors and Guillain-Barre syndrome. The differential diagnosis of facial fasciculations and/or myokymia/NMT is even broader including genetic disorders,