Alessandra Ariatti

Recognition of emotions from visual and prosodic cues in Parkinson’s disease

ObjectiveTo assess whether Parkinson Disease (PD) patients are impaired at perceiving emotions from facial and prosodic cues and whether any putative defective performance concerns recognition of a particular emotion.BackgroundBraak et al. [1] demonstrated that in different stages PD pathology involves the nigrostriatal system, the amygdala, and the insular cortex. Discrete brain lesions to these structures can cause selective deficits in recognising facial and prosodic stimuli expressing particular emotions. However, the investigation of facial and prosodic emotional processing in PD patients has lead to conflicting results.Materials and methodsWe compared 27 cognitively unimpaired PD patients with control subjects by means of the Facial Emotion Recognition Battery and the Emotional Prosody Recognition Battery.ResultsPD patients were impaired in recognising, selecting, and matching facial affects. In particular, the Facial Emotion Recognition Battery demonstrated a severe impairment in recognising sad and fearful faces. In the Emotional Prosody Recognition Battery PD patients demonstrated a diffuse impairment, including the recognition of emotional and propositional prosody.ConclusionsFace emotion processing is impaired in PD patients, with a disproportionate deficit involving fear and sadness. The pattern of face expression processing impairment in PD patients might depend on the regional distribution of the pathology. The widespread involvement of both emotional and propositional prosodic processing parallels the aprosodic characteristics of Parkinsonian speech production.

Parvovirus B19 infection antedating Guillain–Barre’ syndrome variant with prominent facial diplegia

The clinical spectrum of Guillain–Barre syndrome (GBS) has expanded due to variants accounting for benign forms without progression [1–4]. Patients with acute onset of facial diplegia, with or without limb weakness, acral paraesthesias, or areflexia are affected by a regional GBS variant ‘‘facial diplegia and paraesthesias’’ (FDP) [1, 3]. This 36 year old man, 3 weeks after high fever with myalgias, experienced facial pain, difficulty in closing eyes, and pursuing lips. Taste, lacrimation, swallowing, and hearing were normal. On admission (day 2), neurological examination showed facial diplegia and areflexia. Eye movements, strength, coordination, and sensibility were unaffected. By day 4, the patient reported hand numbness. Normal laboratory tests included screening for autoimmune-rheumatic diseases. Virological, microbiological studies excluded a variety of infections (Borrelia burgdorferi, HSV-1/2, VZV, EBV, CMV, HHV-6). Serum IgG and IgM antibodies to gangliosides GM1, GM2, GM1b, GD1a, GD1b, GalNAc-GD1a, GT1a, and GQ1b were investigated (day 3) by enzyme-linked immunosorbent assay (ELISA) as described elsewhere [2, 3]. The antiganglioside antibody assays were negative. CSF (day 5) showed increased protein content (68 mg/dl, normal \ 45). ELISA revealed anti HPV-B19 IgM and IgG (titer above 5.99). Real Time PCR detected a viral load of 28,794 copies/ml. N-PCR showed HPV-B19 DNA in CSF. Electrophysiological study (day 8) showed temporally dispersed peroneal, tibial compound muscle action potentials (1.5–2 mV in amplitude, normal [ 4), border-line slowing in motor conduction (40 m/sec normal [ 45), and delayed peroneal, tibial F-waves (65 ms, normal \ 58). There were proximal conduction blocks in median and ulnar nerves [5]. Sensory fibers were spared. Brain MRI, auditory, and brain stem evoked responses were normal. Intravenous immunoglobulin was started on day 5 (IVIg 0.4 g/kg/daily) and completed over the next five days. By 3 weeks, bifacial weakness and distal numbness had recovered; on day 122, there were neither residual clinical nor electrophysiological abnormalities. ELISA (day 127) showed anti B19 IgM titer lowered to 0.79, whereas IgG remained 5.99 (Biotrin international ltd, Dublin, Ireland).Our patient presented with a post-infectious FDP variant [3]. Major features were albumino-cytologic dissociation and presence of HPV-B19 DNA in serum and CSF during the acute phase. Susuki et al. [3] reported 22 cases with a disease compatible with Ropper’s original description [1]; among those patients, marginal cases were identified without limb paraesthesias or areflexia [3]. Infection serologies during the acute phase evidenced anti-cytomegalovirus, Campylobacter jejuni, Epstein-Barr, Borrelia burgdorferi, and Mycoplasma pneumoniae IgM antibodies in 14 subjects; 13 experienced upper respiratory tract infection. Anti-ganglioside IgM antibodies were detected in five patients. Motor conduction study suggested demyelination in 14 cases and was normal in 7 [3]. HPV-B19 causes erythema infectiosum, aplastic crisis, fetal hydrops, arthritis, vasculitis, and neurological syndromes [6–9]. Skin rashes or arthralgias associated with positive rheumatoid factor and antinuclear antibodies F. Barbi A. Ariatti G. Galassi (&) Department of Neurosciences, University of Modena and Reggio Emilia, Via P. Giardini, 1350, 41010 Modena, Italy e-mail: giulianagalassi@aliceposta.it

Non-convulsive status epilepticus of frontal origin as the first manifestation of Hashimoto's encephalopathy

Hashimoto’s encephalopathy is an often misdiagnosed, life threatening, but treatable, condition which improves promptly with steroid therapy. Since clinical manifestations are heterogeneous and non-specific, the diagnosis is often difficult. Several case reports of Hashimoto’s encephalopathy presenting with partial or generalised seizures are described, but only a few have focused on status epilepticus as the first clinical manifestation. We report two patients presenting with repetitive and prolonged seizures characterised by progressive reduction in contact and reactivity associated with frontal/diffuse polyspike-and-wave activities. This condition, which can be interpreted as a formof non-convulsive status epilepticus (NCSE) of frontal origin, was refractory to antiepileptic drugs but responded promptly to high doses of intravenous steroid treatment. In cases of unexplained encephalopathy with EEG documentation of NCSE, the early recognition and treatment of Hashimoto’s encephalopathy may lead to a favourable prognosis.

Prognostic factors and health-related quality of life in ocular myasthenia gravis (OMG)

We evaluate the factors predictive of prognosis in 91 Caucasian patients affected by ocular myasthenia gravis (OMG), followed at our Institution during an observational time, ranging from 12 to 240 months. The Myasthenia Gravis Foundation of America (MGFA) clinical classification was used to grade the disease severity. We considered as outcome measures the variation in two subscores, ocular (O-QMG) and nonocular (NO-QMG); the last one reflected bulbar, neck, extremity functions. None of the independent variables evaluated for association with the outcome, as age of onset, type of therapy, length of interval between first and last examinations, and presence of antibodies to acetylcholine receptors (AChR-Abs) significantly affected the evolution of O-QMG and of NO-QMG. Health-related quality of life (HRQol) was assessed in 63 patients. Variations of diplopia or ptosis did not affect significantly physical (PCS) or mental composite subscores (MCS) of the Short-Form Health Survey (SF-36). Human leukocyte antigen (HLA) genotyping was studied to explore whether HLA class I and II allelic distribution differed among MG patients and controls. None of the studied HLA alleles significantly differed between OMG patients and controls. Similarly, none of the alleles with frequencies higher than 15% either in OMG patients or in controls was significantly associated, after Bonferroni correction, with the presence or absence of anti-AChR-Abs in serum.

Long-term disability and prognostic factors in polyneuropathy associated with anti-myelin-associated glycoprotein (MAG) antibodies

Aim of the study: Neuropathy associated with IgM monoclonal gammopathy (MGUS) represents distinctive clinical syndrome, characterized by male predominance, late age of onset, slow progression, predominantly sensory symptoms, deep sensory loss, ataxia, minor motor impairment. More than 50% of patients with neuropathy-associated MGUS possess antibodies against myelin-associated glycoprotein (MAG). Purpose of our study was to assess effects on disease progression of demographic, clinical and neurophysiological variables in our large cohort of patients. Materials and Methods: Forty-three Caucasians patients were followed every eight months for median duration time of 93 months. Extremity strength was assessed with Medical Research Council (MRC) Scale, disability with overall disability status scale (ODSS), modified Rankin Scale and sensory function with Inflammatory Neuropathy Cause and Treatment (INCAT) sensory scale (ISS). Statistical analyses were conducted with parametric or non-parametric measures as appropriate. Survival analysis was used to test predictive value of clinical, demographical and neurophysiological variables. Variance analysis was conducted to explain difference on MRC between patients and groups at different time from onset. Results: Results showed that demyelinating pattern, older age and absence of treatment were significant risk factors for disability worsening. No other factors emerged as predictors including gender, ataxia and tremor at baseline, level of anti-MAG and IgM protein concentration in serum. Despite worsening of all outcome measures between first and last visit, quality of life (HRQol) judged by patients did not vary significantly. Conclusions: Our study provides evidence that electrophysiologic pattern, age of onset and absence of treatment are strong predictor of prognosis in anti-MAG polyneuropathy.

Focal sensory-motor status epilepticus in multiple sclerosis due to a new cortical lesion. An EEG–fMRI co-registration study

A case of focal inferior limb sensory-motor status epilepticus as the only manifestation of a multiple sclerosis (MS) relapse is described. To obtain evidence of the relationship between the seizures, the cortical plaque and the left foot motor area, an EEG-fMRI co-registration study was undertaken demonstrating that seizure-related BOLD signal substantially overlapped with the inflammatory lesion involving the foot sensory-motor cortex. Seizures did not respond to intravenous anti-epileptic drugs (AEDs) but were controlled by steroid therapy.

Factors affecting outcome in ocular myasthenia gravis

ABSTRACT Aim of the study: 50%–60% of patients with ocular myasthenia gravis (OMG) progress to generalized myasthenia gravis (GMG) within two years. The aim of our study was to explore factors affecting prognosis of OMG and to test the predictive role of several independent clinical variables. Materials and methods: We reviewed a cohort of 168 Caucasian patients followed from September 2000 to January 2016. Several independent variables were considered as prognostic factors: gender, age of onset, results on electrophysiological tests, presence and level of antibodies against acetylcholine receptors (AChR Abs), treatments, thymic abnormalities. The primary outcome was the progression to GMG and/or the presence of bulbar symptoms. Secondary outcomes were either achievement of sustained minimal manifestation status or worsening in ocular quantitative MG subscore (O-QMGS) or worsening in total QMG score (T-QMGS), assessed by Myasthenia Gravis Foundation of America (MGFA) quantitative scores. Changes in mental and physical subscores of health-related quality of life (HRQoL) were assessed with SF-36 questionnaire. Variance analysis was used to interpret the differences between AChR Ab titers at different times of follow up among the generalized and non-generalized patients. Results: Conversion to GMG occurred in 18.4% of patients; it was significantly associated with sex, later onset of disease and anti-AChR Ab positivity. Antibody titer above the mean value of 25.8 pmol/mL showed no significant effect on generalization. Sex and late onset of disease significantly affected T-QMGS worsening. None of the other independent variables significantly affected O-QMGS and HRQoL. Conclusions: Sex, later onset and anti-AChR Ab positivity were significantly associated with clinical worsening.

C10ORF2 mutation associated with progressive external ophthalmoplegia and clinically isolated syndrome

Sporadic chronic progressive external ophthalmoplegia (CPEO) is most commonly due to large-scale deletions or rearrangements of mitochondrial DNA (mtDNA) [1, 2]. MtDNA mutations are responsible for diseases involving central nervous system, for instance, Leber’s hereditary optic neuropathy (LHON), which is reported in association with both multiple sclerosis (MS) and MS-like magnetic resonance imaging (MRI) patterns, raising important questions about common pathophysiological mechanisms [1–3]. Indeed, mtDNA deletions and respiratory-deficient neurons have been described in MS [4]. Patients presenting first with clinical symptoms, not fulfilling the MRI criteria for dissemination in space and time according to the 2010 revision of the McDonald diagnostic criteria for MS, are classified as clinically isolated syndrome (CIS) possibly antedating definite MS [5]. We report the first case of mitochondrial dysfunction caused by mutation in C10ORF2 gene, presenting with CPEO associated with an incomplete transverse myelitis as CIS [5]. Case report

Coincident chronic inflammatory demyelinating polyneuropathy and focal segmental glomerulosclerosis: a common autoimmunity?

A 40-year-old male developed swallowing difficulties, loss of strength, and imbalance. On admission, the patient exhibited bifacial, extremity weakness, ataxia, impaired sensation, and areflexia. Electrophysiology and nerve biopsy suggested demyelination. Spinal fluid revealed increased protein content. Plasmapheresis showed benefit, but neuropathy relapsed. At second recurrence, urine analysis showed heavy proteinuria. Renal biopsy revealed focal segmental glomerulosclerosis (FSGS). Methylprednisolone and oral cyclophosphamide were given. Long-term steroids and immunoglobulin showed steady benefit. Concurrence of chronic inflammatory demyelinating polyneuropathy and FSGS suggests synergistic cellular and humoral autoimmune mechanisms related to either cross-reactivity within antigenic targets or mimicry between neural and renal epitopes.

Chronic inflammatory demyelinating polyradiculoneuropathy associated with inflammatory bowel diseases: questioning the autoimmunity hypothesis

Dear Editor: Inflammatory bowel diseases (IBD) are chronic disorders encompassing Crohn’s disease (CD) and ulcerative colitis (UC) characterized by abnormal mucosal immune response. Early pathology coincides with intestinal, mesenteric T-cell infiltration, cytokine production, bowel inflammation, and vasculitis. There is evidence that CD4 and CD8 T-cells can trigger autoimmunity when peripherally activated by antigens in a proinflammatory setting. Chronic inflammatory demyelinating polyradiculoneuropathies (CIDP) are caused by immune responses mounted against uncharacterized epitopes. Polyneuropathies associated with IBD exhibit different phenotypes. We studied two patients with CIDP associated with IBD supporting the view of common causality. A 63-year-old woman experienced rectal hemorrhage, acral numbness, and unsteady gait during acute hepatitis. Intestinal biopsy diagnosed CD. Neurologic examination showed absent jerks and distal loss of all sensory modalities. Muscle strength was minimally affected. Normal laboratory results included B12, E vitamin serum level, tumor markers, microbial, and immunological screenings. Sural-evoked responses were either absent or diminished in amplitude with slowed velocity. There were prolonged F wave and distal latencies of median, tibial, and peroneal muscle action potentials. Sural biopsy showed fiber loss and demyelination in 30% of fibers teased. Onion bulbs and mononuclear inflammatory cells were absent. Patient was treated with long-term steroids. On clinical follow-up, her neurological disability progressed in the absence of CD recurrence. Sixteen years after onset, distal strength was graded 3/5, whereas ataxia was marked and distal sensation was severely impaired. Electrophysiology confirmed demyelination. The second patient when aged 33 was diagnosed having UC. Twelve months later, he developed acral paresthesias and extremity weakness graded 3/5 on examination. Deep jerks were unevokable; Romberg sign was positive, and touch and deep sensation was distally impaired. In nerve conduction, there were partial motor conduction block, abnormal temporal dispersion, and diminished velocity along median, ulnar, peroneal, and tibial nerves. Patient refused spinal tap. Treatment with metronidazole was not given. Repeated courses of intravenous immuneglobulins had benefit. Our patients presented common features of moderate distal rather than proximal weakness and ataxia due to proprioceptive sensory loss. Electrophysiology suggested in both ongoing multifocal demyelination, which was histologically proven in case 1. Neurological illness began acutely in patient 1 at CD onset, raising the question of a sensory variant of acute inflammatory demyelinating polyradiculoneuropathy or of CIDP with acute onset. UC of case 2 predated by 12 months his neuropathy, which improved with immunemodulating therapy and ultimately relapsed. Gondim et al. reported seven CIDP cases associated in three with CD and in four with UC: The three CD had more proximal than distal Int J Colorectal Dis (2009) 24:603–604 DOI 10.1007/s00384-009-0646-x