Massimo Marianetti

Neurocognitive Dysfunction in Systemic Lupus Erythematosus: Association with Antiphospholipid Antibodies, Disease Activity and Chronic Damage

Introduction Systemic lupus erythematosus (SLE) is characterized by frequent neuropsychiatric involvement, which includes cognitive impairment (CI). We aimed at assessing CI in a cohort of Italian SLE patients by using a wide range of neurocognitive tests specifically designed to evaluate the fronto-subcortical dysfunction. Furthermore, we aimed at testing whether CI in SLE is associated with serum autoantibodies, disease activity and chronic damage. Methods Fifty-eight consecutive patients were enrolled. Study protocol included data collection, evaluation of serum levels of ANA, anti-dsDNA, anti-cardiolipin, anti-β2-glycoprotein I, anti-P ribosomal, anti-endothelial cell, and anti-Nedd5 antibodies. SLEDAI-2000 and SLICC were used to assess disease activity and chronic damage. Patients were administered a test battery specifically designed to detect fronto-subcortical dysfunction across five domains: memory, attention, abstract reasoning, executive function and visuospatial function. For each patient, the raw scores from each test were compared with published norms, then transformed into Z scores (deviation from normal mean), and finally summed in the Global Cognitive Dysfunction score (GCDs). Results Nineteen percent of patients had mild GCDs impairment (GCDs 2–3), 7% moderate (GCDs 4–5) and 5% severe (GCDs≥6). The visuospatial domain was the most compromised (MDZs = −0.89±1.23). Anti-cardiolipin IgM levels were associated with visuospatial domain impairment (r = 0.331, P = 0.005). SLEDAI correlated with GCDs, and attentional and executive domains; SLICC correlated with GCDs, and with visuospatial and attentional domains impairment. Conclusions Anti-phospholipids, disease activity, and chronic damage are associated with cognitive dysfunction in SLE. The use of a wide spectrum of tests allowed for a better selection of the relevant factors involved in SLE cognitive dysfunction, and standardized neuropsychological testing methods should be used for routine assessment of SLE patients.

Neurological Involvement in Primary Sjögren Syndrome: A Focus on Central Nervous System

Objectives Sjögren syndrome is an autoimmune disease involving mainly salivary and lacrimal glands. Beyond widely described PNS involvement, high variable prevalence of CNS manifestations ranging from 2.5 and 60% of all pSS patients has been reported, without specific syndrome definition. The aim of this cohort study was to evaluate the prevalence of CNS signs and symptoms in pSS patients and to identify possible biomarkers of CNS damage. Methods 120 patients with pSS diagnosis according to the 2002 American-European Consensus Group criteria were enrolled after exclusion of secondary causes. All patients underwent to a wide neurological, neuropsychological, psychiatric, neuroradiological and ultrasonographic evaluation. Results Central and peripheral nervous system involvement was observed in 81 patients with a prevalence of 67.5%. The prevalence of CNS involvement was significantly higher than PNS disease (p 0.001). 68 patients (84%) shown non-focal CNS symptoms and 64 (79%) focal CNS deficits with headache as the most common feature (46.9%), followed by cognitive (44.4%) and mood disorders (38.3%). Particularly, we observed a high prevalence of migraine without aura, subcortical frontal executive functions and verbal memory impairment and apathy/alexythimia. MR spectroscopy revealed a reduction of NAA levels or NAA/Cr ratio decrease in subcortical frontal and basal ganglia white matter, while ultrasonography showed an impairment of microvasculature response. At multivariate analysis, headache, cognitive disorders and psychiatric symptoms was significantly associated to serological markers (anti-SSA), MRS and ultrasonographic features. Conclusions The higher prevalence of MWO-mimic headache, cognitive dys-esecutive syndrome and mood disorders observed in this series confirmed previous evidences of a higher diffused CNS compromission rather than focal involvement such as SM-like clinical course or NMO-like syndrome. The association with immunological biomarkers, metabolic cerebral dysfunction and microvascular damage suggests a possible endothelial dysfunction of the cerebral microcirculation or a potential inflammation-mediated shift of the neurovascular coupling.

Clinical, neuropsychological, neurophysiologic, and genetic features of a new Italian pedigree with familial cortical myoclonic tremor with epilepsy.

We studied the clinical, neuropsychological, neurophysiologic, and genetic features of an Italian family with familial cortical myoclonic tremor with epilepsy (FCMTE). Clinically affected members of the family had limb and voice tremor, seizures, and myoclonus involving the eyelids during blinking. Neuropsychological testing disclosed visuospatial impairment, possibly due to temporal lobe dysfunction. Neurophysiologic findings suggested increased primary motor cortex excitability with normal sensorimotor integration. Linkage analysis excluded the 8q24 locus, where patients shared a common haplotype spanning 14.5 Mb in the pericentromeric region of chromosome 2.

Tests for the evaluation of depression in the elderly: A systematic review

The incidence of depression in the elderly has risen in recent years, with 30% of people over the age of 65 now reported to suffer from mood disorders. There are a number of possible causes for this increase; moreover, as the symptoms of depression in the elderly are often difficult to identify and interpret, a diagnosis of depression in the elderly may be difficult to make, particularly when other concomitant pathologies mask the signs and symptoms of this disease. There is thus a need to standardize the various self-rating and hetero-evaluation scales used to differentiate between normal and depressed subjects. These tools are designed to investigate and evaluate the various components of depression in depth. They are essential for the diagnosis and therapy in patients who suffer from mood disorders, though it should be borne in mind that these tests need to be preceded and confirmed by a thorough psychiatric examination.

Endoscopic findings and psychometric abnormalities: What is the relationship in upper endoscopic outpatients?

BACKGROUND Psychological disorders are often associated with diseases of the upper digestive tract. Although emotions can influence gastrointestinal function in healthy individuals, psychological setting in upper gastrointestinal patients are unclear. We evaluate the psychological alterations prevalence in outpatients submitted to upper endoscopy. MATERIALS AND METHODS A total of 130 patients (50 males and 80 females; mean age 54±17 years) submitted to upper gastrointestinal endoscopy, were enrolled over the period May 2009 - September 2010. Subjects were asked to complete questionnaires before endoscopic examination. Alexithymia, anxiety, depression and coping style were assessed using the Toronto Alexithymia Scale, Spielberger Trait Anxiety Inventory, Beck Depression Inventory and Coping Inventory for Stressful Situations, respectively. RESULTS Coping impairment, Alexithymia, Anxiety and Depression were found respectively in 80.3%, 25.4%, 24.6% and 17.2%, often in association. Task-oriented, emotion-oriented and avoidance-oriented alterations were found in 41.8%, 40% and 30.6%, respectively. No correlations were demonstrated between diagnosis of upper gastrointestinal disease and psychometric results. CONCLUSIONS In our study, a high prevalence of psychometric alterations in gastrointestinal outpatients was unconnected with endoscopic findings, especially considering coping style alterations. This aspect should be taken into account in patients management and a long-term follow-up should clarify a possible role of these factors in patients prognosis and compliance.

Hemiballismus in subthalamic haemorrhage: efficacy of levetiracetam

Sir, A 65-year-old man with uncontrolled hypertension presented with severe ataxia, dizziness and vomiting in January 2005. Magnetic resonance imaging (MRI) brain showed a hyperintense haemorrhagic lesion in the cerebellar vermis on T2weighted images (Fig. 1a) and heterogeneous popcorn-like lesions with a mixed signal core in fast field echo sequences, which were consistent with multiple cavernous angiomas (Fig. 1b). As cavernous angiomas are typically occult at angiography, digital subtraction angiography was deemed unnecessary. Upon admission, high arterial blood pressure values (ABP, mean values 210/110 mmHg) were rapidly controlled with quinalapril 20 mg/ day and hydrochlorothiazide 25 mg/day. Full blood count, erythrocyte sedimentation rate, serum electrolytes, routine autoantibodies, glycaemia, liver and kidney function tests were within normal limits. Three days after admission, the patient presented with two consecutive episodes of severe vomiting and marked increase in ABP (200/100 mmHg) followed by sudden onset of severe involuntary, forceful flailing and wide movements in the left arm and leg. Large, prevalently proximal, vigorous and kicking movements were subcontinuously present during the waking hours, enhanced by voluntary movement of the involved limb and reduced or absent during sleep. A second MRI brain showed a markedly hyperintense haemorrhagic area in fluid attenuated inversion recovery (FLAIR) and T2-weighted images in the right subthalamic nucleus (STN, Fig. 1c). A diagnosis of hemiballismus related to subthalamic haemorrhage was considered. The patient was treated with haloperidol (8 mg/day) and lorazepam (5 mg/day), which led to a rapid improvement in the involuntary movements over a few days and an increasing degree of sedation and stiffness. Treatment was thus discontinued after 1 week; although rigidity and somnolence remitted rapidly, involuntary movements relapsed at 2-week evaluation. Levetiracetam (LEV) was started at a dosage of 125 mg twice daily and increased by 125 mg every week. A significant improvement in the hemiballismus was observed at 4 weeks (1000 mg), followed by complete remission when a final dose of 2000 mg/day was reached. At the 3-month follow-up, LEV was decreased by 125 mg per week to assess a possible long-term spontaneous improvement. As hemiballismus relapsed after a reduction of 1000 mg, LEV dosage was again raised to the previous dose with subsequent improve of involuntary movements.

Cognitive dysfunction improves in systemic lupus erythematosus: Results of a 10 years prospective study

Objective Cognitive impairment (CI) has been described in 3–80% of Systemic lupus erythematosus (SLE) patients but only short-term studies evaluated its over-time changes, suggesting that CI is usually a stable finding. We aimed at evaluating the changes of SLE-related CI in a 10-years prospective single center cohort study. Methods We evaluated 43 patients (M/F 5/38; mean age = 45.7±10.1 years; mean disease duration = 230.8±74.3 months) at baseline (T0) and after 10 years (T1). A test battery designed to detect fronto-subcortical dysfunction across five domains (memory, attention, abstract reasoning, executive and visuospatial function) was administered. A global cognitive dysfunction score (GCD) was obtained and associated with clinical and laboratory features. Results Prevalence of CI was 20.9% at T0 and 13.9% at T1 (P = NS). This impairment was prevalently mild at T0 (55.5%) and mild or moderate at T1 (36.3% for both degrees). After 10 years, CI improved in 50% of patients, while 10% worsened. Impaired memory (P = 0.02), executive functions (P = 0.02) and abstract reasoning (P = 0.03) were associated with dyslipidemia at T0. Worsening of visuospatial functions was significantly associated with dyslipidemia and Lupus Anticoagulant (P = 0.04 for both parameters). Finally, GCD significantly correlated with chronic damage measured by SLICC/damage index at T0 (r = 0.3; P = 0.04) and T1 (r = 0.3; P = 0.03). Conclusions For the first time, we assessed CI changes over 10-years in SLE. CI improved in the majority of the patients. Furthermore, we observed an improvement of the overall cognitive functions. These results could suggest that an appropriate management of the disease during the follow-up could be able to control SLE-related CI.

Recognition and naming of famous buildings: Italian normative data

Semantically unique items are concrete entities characterized by a unique cluster of semantic information. In this field, neuropsychology has always given more attention to faces than to other kind of stimuli. An important category that has been largely neglected so far is famous buildings. A total of 200 healthy Italian adults with age, sex and education homogenously distributed across subgroups were administered a famous buildings naming and recognition test, which assessed both visual and verbal modalities. The test was divided in seven sections; norms were calculated taking into account demographic variables such as age, sex and education. Multiple regression analyses showed that education influenced significantly the performance on all subtests; age had a significant effect for five subtests; sex for three subtests. Adjusted scores were used to determine inferential cutoff scores and to compute equivalent scores.

Single strategic infarct dementia mimicking dementia with Lewy bodies.

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