MRI Planimetry and Magnetic Resonance Parkinsonism Index in the Differential Diagnosis of Patients with Parkinsonism.

BACKGROUND AND PURPOSE: Differential diagnosis of multiple system atrophy, progressive supranuclear palsy, and corticobasal degeneration from Parkinson disease on clinical grounds is often difficult. MR imaging biomarkers could assist in a more accurate diagnosis. We examined the utility of MR imaging surface measurements (MR imaging planimetry) in the differential diagnosis of patients with parkinsonism. MATERIALS AND METHODS: Fifty-two patients with Parkinson-plus (progressive supranuclear palsy, n = 24; corticobasal degeneration, n = 9; multiple system atrophy, n = 19), 18 patients with Parkinson disease, and 15 healthy controls were included. Corpus callosum, midbrain, and pons surfaces; relevant indices; and the Magnetic Resonance Parkinsonism Index were calculated. Corpus callosum subsection analysis was performed, and the corpus callosum posteroanterior gradient was introduced. RESULTS: A Magnetic Resonance Parkinsonism Index value of >12.6 discriminated progressive supranuclear palsy from other causes of parkinsonism with a 91% sensitivity and 95% specificity. No planimetry measurement could accurately discriminate those with multiple system atrophy with parkinsonism from patients with Parkinson disease. A corpus callosum posteroanterior gradient value of ≤191 was highly specific (97%) and moderately sensitive (75%) for the diagnosis of corticobasal degeneration versus all other groups. A midbrain-to-corpus callosum posteroanterior gradient ratio of ≤0.45 was highly indicative of progressive supranuclear palsy over corticobasal degeneration (sensitivity 86%, specificity 88%). CONCLUSIONS: MR imaging planimetry measurements are potent imaging markers of progressive supranuclear palsy and promising markers of corticobasal degeneration but do not seem to assist in the diagnosis of multiple system atrophy with parkinsonism.

Intermittent Atrioventricular Block following Fingolimod Initiation.

A 47-year-old female patient with multiple sclerosis (MS) developed symptomatic intermittent 2nd degree atrioventricular block (AVB) of five-hour duration, five hours after the first two doses of fingolimod, that resolved completely. Frequency domain analysis of heart rate variability (HRV) revealed increased parasympathetic activity and decreased sympathetic tone, while modified Ewing tests were suggestive of impaired cardiac sympathetic function. We hypothesize that expression of this particular arrhythmia might be related to autonomic nervous system (ANS) dysfunction due to demyelinating lesions in the upper thoracic spinal cord, possibly augmented by the parasympathetic effect of the drug.

Genetic assessment of familial and early-onset Parkinson's disease in a Greek population.

BACKGROUND AND PURPOSE: Although the first mutation associated with Parkinson's disease (PD) was identified several years ago in the alpha-synuclein (SNCA) gene in families of Greek and Italian ancestry, a more systematic study of this and other known PD mutations has not been performed in the Greek population. METHODS: A genetic analysis in 111 familial or sporadic with early-onset (≤50 years, EO) PD patients was performed for the presence of the A53T SNCA mutation. In separate subgroups of these patients, further mutations in the SNCA, LRRK2, Parkin, PINK1 and DJ-1 genes were searched for. Additionally, a subgroup of familial cases was analysed for mutations in the glucocerebrosidase (GBA) gene. RESULTS: In total, five patients (4.5% of our whole population) were identified with the A53T SNCA mutation, two with a heterozygote dosage mutation and one with a heterozygote point mutation in the Parkin gene, and seven patients (10.3% of our familial cohort) with GBA gene mutations. CONCLUSIONS: The A53T mutation in the SNCA gene, although uncommon, does represent a cause of PD in the Greek population, especially of familial EOPD with autosomal dominant inheritance. GBA mutations in the familial cohort tested here were as common as in a cohort of sporadic cases previously examined from the same centres. For the remainder of the genes, genetic defects that could definitively account for the disease were not identified. These results suggest that further Mendelian traits that lead to PD in the Greek population remain to be identified.

Relationship of intensity and special characteristics of migraine to depressive and anxious features.

Mood and pain are interrelated to each other in a mutual and complex manner. Patient populations in headache clinics exhibit more emotional disturbance than general practice patients. Nonetheless, the degree of psychological illness among headache patients is less than maybe found in psychiatric outpatients. However, it is a fact that several psychiatric disorders appear to be comorbid with primary headache syndromes such as migraine. Still, prospective standardized studies are sparse. We aimed to investigate whether migraine per se or specific migraine characteristics are associated to depression and anxiety. In a single center study (Department of Neurology of the University of Athens) migraineurs were asked for several headache features such as pain intensity, attack frequency, average attack duration, prodromal symptoms and the presence of aura. We assessed 50 consecutive headache patients who were referred to our headache outpatient clinic. Patients diagnosed with non-migraine syndromes, mixed non-migraine and migraine syndromes, or patients with previously diagnosed systemic disease known to precipitate psychiatric disorders (such as systemic lupus erythematodes) were excluded from the study. Furthermore, we did not include any subjects who were already on antidepressive or other psychiatric medication. Twenty four patients met the inclusion criteria. The data were then correlated with scores obtained by the Beck Depression Inventory and the Hamilton's scales for Depression and Anxiety. Our results showed an increased frequency of mild and moderate depression compared to what was expected from the normal population which is in line with past observations on headache patients. In an analogous manner, mild and moderate anxiety appeared more frequently among migraineurs than healthy subjects. However, we did not find any significant relation between depression or anxiety and parameters such as pain intensity, monthly attack frequency, attack duration, presence or absence of aura, appearance of pre-ictal prodromal symptoms and migraine career duration (age of assessment minus age of migraine onset). These findings suggest that migraine, although often comorbid with depression and anxiety, has no specific headache characteristics causally related to mood abnormalities. Larger samples will be required in future studies to address the question of a link between more specific mood and mental disturbances with primary headache syndromes.

Prevalence of cerebrospinal fluid oligoclonal IgG bands in Greek patients with clinically isolated syndrome and multiple sclerosis.

UNLABELLED: Lower prevalence of cerebrospinal fluid oligoclonal IgG bands (IgG-OCBs) has been reported in multiple sclerosis (MS) patients from Southern Europe compared to other western countries. OBJECTIVES: We aimed to determine the prevalence of CSF OCBs in Greek MS patients and to examine their relation with some selected clinical and demographical features. METHODS: Included patients fulfilled the 2005 McDonald criteria for definite MS (CDMS) or clinically isolated syndrome (CIS) and had a spinal tap performed between 2006 and 2010. Paired CSF and plasma samples were analyzed using isoelectric focusing followed by IgG-specific immunofixation. A pattern of two or more bands present only in the CSF was defined as positive. OCB status was correlated with age at disease onset, initial symptomatology, relapse rate, disease subtype, disease duration, medication, EDSS score and MSSS. RESULTS: Of the 231 included patients (53.2% with CDMS and 48.6% with CIS) 67.5% had OCBs. The prevalence of positive patterns did not differ between CIS and CDMS patients (67.6% vs. 67.5%, respectively). OCB-positive patients were younger than OCB-negative patients (35.2±10.3 vs. 38.7±11.8 years respectively, p=0.022) and had more frequently cervical spinal cord lesions (x2=7.08, p=0.008). No difference was observed between the two subgroups in the other studied disease parameters. CONCLUSION: Despite the lower frequency of positive IgG-OCB patterns in our patients, both subgroups were mostly similar with regard to their clinical and demographic characteristics suggesting that the OCB status lacks prognostic significance in MS.

Demyelinating Disease following Anti-TNFa Treatment: A Causal or Coincidental Association? Report of Four Cases and Review of the Literature.

Tumor necrosis factor antagonists (anti-TNFa) are an established therapeutic option for several autoimmune and inflammatory bowel diseases. Despite their clinical effectiveness, neurological adverse events have been reported and literature data suggest a potential role of anti-TNFa in the induction of demyelination of the CNS. We present four patients treated with anti-TNFa who developed symptoms suggestive of CNS demyelination. The first patient, a 17-year-old male who received etanercept for psoriatic arthritis for eight months, presented with dysesthesias up to T4 level. The second patient, a 30-year-old male treated with adalimumab for three years due to ankylosing spondylitis, presented with right unilateral tinnitus. The third case, a 47-year-old female, received etanercept for four years because of psoriatic arthritis and developed persistent headache and left-sided face and head numbness. Finally, the fourth patient, a 57-years-old female treated with etanercept for six years due to ankylosing spondylitis, presented with difficulty in speech, swallowing, and ptosis of the right corner of the mouth. In all cases, brain MRI showed lesions suggestive of demyelination, while positive oligoclonal bands were detected in the CSF. Anti-TNFa treatments were discontinued and patients showed clinical improvement with pulsed intravenous corticosteroid therapy. CNS demyelination following anti-TNFa treatment represents a relatively rare but potential serious complication. Close follow-up and MRI monitoring of these patients is mandatory to elucidate whether the clinical manifestations represent adverse events occurring during anti-TNFa therapy or a first demyelinating episode.

The hygienist and sociologist Louis-René Villermé (1782-1863): a pioneer of occupational medicine.

BACKGROUND: Louis-René Villermé's work and research have ranked him among the most important figures in the history of occupational medicine. OBJECTIVES: The aims of this article were to objectively record the influence and the impact of Villermé's life and work on the establishment of occupational medicine. METHODS: A thorough analysis of scientific and historical literature on the subject was conducted. The authors paid special attention to primary French sources. RESULTS: Louis-René Villermé was born in Paris in 10 March 1782. Taking advantage of his good fortune and financial prosperity, due to the recognition of his initial work, he progressed efficiently and with decision towards a new way of thinking. He stressed the importance of observation of the social environment, the role of investigations on lack of hygiene, the significance of statistical recording and the study of demographic statistics, and devoted himself to the labour force's health problems. He died in his homestead on 16 November 1863. CONCLUSIONS: Villermé lived an intense life full of activity, social work and travel. His support of the working classes' rights, his opposition to child labour and gender inequality, and his fight for humane conditions in prisons remain diachronic ideals. He provided a reference model for socio-medical research and contributed to the establishment of the new scientific discipline, Occupational Medicine.

Sir Robert Carswell (1793-1857): coining the term "melanoma".

Melanoma is a neoplastic disorder produced by malignant transformation of the normal melanocyte, accounting for 4% of all skin malignancies. This malignancy was described since antiquity as a "fatal black tumour". In the 19th century, the distinguished pathologist Sir Robert Carswell coined first the term melanoma, provided its pathological description and depicted the lesion in his famous work Pathological Anatomy: Illustrations of the elementary forms of disease.

Clovis Vincent (1879-1947): founder of French neurosurgery and promoter of oncologic neurosurgery.

The eminent neurologist Clovis Vincent decided to become neurosurgeon at an advanced age. His is considered the founder of French neurosurgery and the Europe's first neurosurgeon. He was mainly interested in pituitary tumors and his work on oncologic neurosurgery remains valuable.

[Sexual mutilations through ages]. / Les mutilations sexuelles à travers les âges.

Among the ethnic mutilations (volunteer mutilations performed for religious, aesthetic, moral or hygienic purposes), genital mutilation (circumcision, castration, total emasculation, infibulation, excision, etc.) have always fascinated the human mind and are the subject of our historical overview.

A neurologist in the origin of European and International neurosurgery: Clovis-Julien-Désiré Vincent (1879-1947).

Vincent Clovis began his carrier as a neurologist and finally became neurosurgeon at an advanced age. He is considered the founder of French neurosurgery, and after Harvey Williams Cushing, Europe's first neurosurgeon. He was mainly interested in pituitary tumors, in cerebral abscesses and in cerebral oedema.

Joseph-Claude-Anthelme Récamier (1774-1852): forerunner in surgical oncology.

Professor J.C.A. Récamier (1774-1852), the undisputed founder of modern gynecologic surgery, had also excelled in the field of oncology. In particular, he performed the first successful vaginal hysterectomy for cancer; he conducted extensive research on cancer metastatic process and he was the proponent of a cancer treatment method by compression.

The Nobel Prize laureate - father of anaphylaxis Charles-Robert Richet (1850-1935) and his anticancerous serum.

Professor of physiology Charles-Robert Richet, winner of the Nobel Prize in 1913, is best known for his work on anaphylaxis. However, with his collaborator Jules Héricourt studied the effects of antibody treatment and made the very first attempts to fight cancer with serotherapy. Being versatile, Richet contributed in neurology, psychology and was also a poet, playwrighter, pacifist and pioneer in aviation.

Association of reversed Robin Hood syndrome with risk of stroke recurrence.

BACKGROUND: Reversed Robin Hood syndrome (RRHS) has recently been identified as one of the mechanisms of early neurologic deterioration in acute ischemic stroke (AIS) patients related to arterial blood flow steal from ischemic to nonaffected brain. We sought to investigate the association of RRHS with risk of stroke recurrence in a single-center cohort study. METHODS: Consecutive patients with AIS or TIA affecting the anterior circulation were prospectively evaluated with serial NIH Stroke Scale assessments and bilateral transcranial Doppler monitoring with breath-holding test. RRHS was defined according to previously validated criteria. RESULTS: A total of 360 patients (51% women, mean age 62 ± 15 years) had an ischemic stroke (81%) or TIA (19%) in the anterior circulation, and 30 (8%) of them had RRHS. During a mean follow-up period of 6 months (range 1-24), a total of 16 (4%) recurrent strokes (15 ischemic and 1 hemorrhagic) were documented. The cumulative recurrence rate was higher in patients with RRHS (19%; 95% confidence interval [CI] 1-37) compared to the rest (15%; 95% CI 0-30; p = 0.022 by log-rank test). All recurrent strokes in patients with RRHS were cerebral infarcts that occurred in the ipsilateral to the index event anterior circulation vascular territory. After adjusting for demographic characteristics, vascular risk factors, and secondary prevention therapies, RRHS was independently associated with a higher stroke recurrence risk (hazard ratio 7.31; 95% CI 2.12-25.22; p = 0.002). CONCLUSIONS: Patients with AIS and RRHS appear to have a higher risk of recurrent strokes that are of ischemic origin and occur in the same arterial territory distribution to the index event. Further independent validation of this association is required in a multicenter setting.

Multicenter external validation of the ABCD2 score in triaging TIA patients.

OBJECTIVES: A simple clinical score (ABCD(2) score) has been introduced to triage TIA patients with a high early risk of stroke. External validation studies have yielded inconsistent results regarding the predictive ability of the ABCD(2) score. We aimed to prospectively validate the former score in a multicenter case series study. METHODS: We prospectively calculated the ABCD(2) score (age [> or = 60 years: 1 point]; blood pressure [systolic >140 mm Hg or diastolic >90 mm Hg: 1[; clinical features [unilateral weakness: 2, speech disturbance without weakness: 1, other symptom: 0]; duration of symptoms [ <10 minutes: 0, 10-59 minutes: 1, > or = 60 minutes: 2]; diabetes mellitus [yes: 1]) in consecutive TIA patients hospitalized in 3 tertiary care neurology departments across 2 different racial populations (white and Asian). RESULTS: The 7-day and 90-day risks of stroke in the present case series (n = 148) were 8% (95% CI 4%-12%) and 16% (95% CI 10%-22%). The ABCD(2) score accurately discriminated between TIA patients with high 7-day (c statistic 0.72, 95% CI 0.57-0.88) and 90-day (c statistic 0.75, 95% CI 0.65-0.86) risks of stroke. The 90-day risk of stroke was 7-fold higher in patients with an ABCD(2) score >3 points (28%, 95% CI 18%-38%) than in patients with an ABCD(2) score < or = 3 points (4%, 95% CI 0%-9%). After adjustment for stroke risk factors, race, history of previous TIA, medication use before the index TIA and secondary prevention treatment strategies, an ABCD(2) score of >2 was associated with a nearly 5-fold greater 90-day risk of stroke (hazard ratio 4.65, 95% CI 1.04-20.84, p = 0.045). CONCLUSION: Our findings externally validate the usefulness of the ABCD(2) score in triaging TIA patients with a high risk of early stroke in a multiethnic sample of hospitalized patients. The present data support current guidelines endorsing the immediate hospitalization of patients with an ABCD(2) score >2.

Measurement of autonomic dysregulation in multiple sclerosis.

OBJECTIVE: Patients with definite multiple sclerosis (MS) were tested for autonomic nervous system (ANS) dysfunction using clinical symptomatology criteria and non-invasive laboratory testing. Exactly 45.45% of patients exhibited subjective symptoms of autonomic dysfunction and 42.42% of patients had abnormal laboratory tests results. METHODS: The sympathetic ANS tests were abnormal in 30.3% of MS patients and the parasympathetic ANS tests were abnormal in 18.18% of MS patients. The most sensitive test for the presence of autonomic dysfunction was the sympathetic skin response. CONCLUSION: Autonomic dysfunction was often subclinical and we conclude that it is preferable to combine several tests for a more thorough and accurate evaluation of the ANS impairment in MS.

Central nervous system manifestations of Mycoplasma pneumoniae infections.

Mycoplasma pneumoniae infection is associated with several manifestations from the central nervous system (CNS) such as encephalitis, aseptic meningitis, acute transverse myelitis, stroke, and polyradiculopathy. In the current paper epidemiologic, clinical, laboratory and treatment data on these manifestations are reviewed. The M. pneumoniae induced immune dysregulation and its contributing role in the pathogenesis of neurological insult is discussed. The recent introduction in clinical practice of newer molecular diagnostic techniques has helped in establishing a firmer association between M. pneumoniae infection and CNS disease especially encephalitis. Clinicians should be aware of the potential association between M. pneumoniae infection and several CNS manifestations. The role of various anti-microbial or immunomodulating therapies in treating such manifestations should be further explored.