Neoplastic meningitis from solid tumors: a prospective clinical study in lombardia and a literature review on therapeutic approaches.

Neoplastic dissemination to the leptomeninges is an increasingly common occurrence in patients with both haematological and solid tumors arising outside the central nervous system. Both refinement of diagnostic techniques (Magnetic resonance imaging) and increased survival in patients treated with targeted therapies for systemic tumors account for this increased frequency. Cerebrospinal fluid cytological analysis and MRI confirm clinical diagnosis based on multifocal central nervous system signs/symptoms in a patient with known malignancy. Overall survival in patients with leptomeningeal neoplastic dissemination from solid tumors is short, rarely exceeding 3-4 months. However, selected patients may benefit from aggressive therapies, Apart from symptomatic treatment, intrathecal chemotherapy is used, with both free (methotrexate, Thiotepa, AraC) and liposomal antitumor agents (liposomal AraC). Palliative radiotherapy is indicated only in cases of symptomatic bulky disease, surgery is limited to positioning of Ommaya recervoirs or C5F shunting. We report clinical data on a cohort of 26 prospectively followed patients with neoplastic leptomeningitis followed in Lombardia, Italy, in 2011. Prognostic factors and pattern of care are reported.

Stereotypic behaviors in degenerative dementias.

Stereotypies are simple or complex involuntary/unvoluntary behaviors, common in fronto-temporal dementia (FTD), but not studied in other types of degenerative dementias. The aim was to investigate stereotypy frequency and type in patients with FTD, Alzheimer's disease (AD), progressive supranuclear palsy (PSP) and Parkinson's disease with dementia (PDD) in a multicenter observational study; and to investigate the relation of stereotypies to cognitive, behavioral and motor impairment. One hundred fifty-five consecutive outpatients (45 AD, 40 FTD, 35 PSP and 35 PDD) were studied in four hospitals in northern Italy. Stereotypies were examined by the five-domain Stereotypy Rating Inventory. Cognition was examined by the Mini Mental State and Frontal Assessment Battery, neuropsychiatric symptoms by the Neuropsychiatric Inventory, and motor impairment and invalidity by the Unified Parkinson's Disease Rating Scale part III, and activities of daily living. Stereotypies were present in all groups. FTD and PDD had the greatest frequency of one-domain stereotypies; FTD also had the greatest frequency of two-or-more domain stereotypies; movement stereotypies were the most common stereotypies in all groups. AD patients had fewer stereotypies than the other groups. Stereotypies are not exclusive to FTD, but are also fairly common in PSP and PDD, though less so in AD. Stereotypies may be underpinned by dysfunctional striato-frontal circuits, known to be damaged in PSP and PDD, as well as FTD.

Frequency and clinical features of Lewy body dementia in Italian memory clinics.

BACKGROUND: The latest developments in Lewy Body Dementia (DLB) raise some controversies on clinical features, neuroimaging and therapy. The aim of our study is to determine clinical, neuropsychological, neuroimaging and EEG profile of DLB through retrospective and prospective data of 102 patients. METHODS: data were collected with an analytical form that was developed by an expertise of neurologists. RESULTS: DLB represented 4.8% of the dementia population, with no sex difference. Family history of dementia was common (24.5%), while familiarity for parkinsonism was rare (4.9%). Cognitive disturbances were the predominant clinical presentation at onset (49%), followed by behavioral symptoms (29.4%) and parkinsonism (21.6%). Clinical features at consultation were: memory disturbances (almost all cases), symmetrical (68.6%) or asymmetrical (18.6%) parkinsonism, cognitive fluctuations (49%), visuospatial deficits (53.9%), and visual hallucinations (44.1%). Autonomic signs were present in a third of the cases, while sleep disorders were present in 44.1%. Some clinical response to antiparkinsonian drugs was evident in half of the cases. MRI, SPET, EEG and Neuropsychiatric Inventory data were available in a subgroup of patients. CONCLUSIONS: Most of our data were in accordance with the previous literature. However, some data underline the relationship between DLB, Alzheimer's and Parkinson's disease.

Bilateral intracavernous carotid artery aneurysms presenting as abducens nerve palsy: case report.

Bilateral intracavernous carotid artery aneurysms are very rare and can be usually observed in patients with multiple intracranial aneurysms. Here we present the case of a 73 year-old woman who experienced worsening diplopia due to progressive bilateral paresis of the lateral rectus muscles. Computed tomography (CT) and magnetic resonance imaging (MRI) examinations showed bilateral roundish parasellar and intracavernous masses, with homogeneous contrast-enhancement and absence of subarachnoid haemorrhage (SAH). Cerebral angiography revealed bilateral aneurysms of the intracavernous carotid artery. Once considered the age of the patient, the anatomical features of the aneurysms and the risks of traditional or endovascular surgery, we decided not to proceed to any treatment other than the orthoptic correction of the diplopia and the careful correction of arterial hypertension. We provide a brief review of the literature on bilateral intracavernous aneurysms and a discussion about their treatment.

Clinical and neuroradiological aspects of Sneddon's syndrome and primary antiphospholipid antibody syndrome. A follow-up study.

We performed a study to investigate differences and similarities between patients with Sneddon's syndrome and those with primary antiphospholipid syndrome (PAS), by clinical follow-up, magnetic resonance imaging (MRI) and angiography. Nine patients with Sneddon's syndrome and 11 patients with PAS were assessed at diagnosis and followed for a mean of 6 years. The clinical and MRI findings indicated that Sneddon's syndrome and PAS are distinct entities. Patients with Sneddon's syndrome had a progressive clinical course with increasing disability and cognitive deterioration; patients with PAS had a more benign course. Infarcts in territories of the main cerebral arteries were frequent in PAS, while leukoaraiosis and small lacunar infarcts were more common in Sneddon's syndrome. In 3 of 7 women initially diagnosed with PAS, the diagnosis was changed to systemic lupus erythematosus during follow-up. Differential diagnosis of Sneddon's syndrome and PAS is important, as early therapy is effective for the latter, more benign, condition.

Affective symptoms in multiple system atrophy and Parkinson's disease: response to levodopa therapy.

The objective was to determine the extent to which psychiatric disturbances (especially mood disorders) generally considered poor prognostic factors, are present in patients with striatonigral (SND) type multiple system atrophy (MSA) compared with patients with idiopathic Parkinson's disease (IPD). The Hamilton depression scale (HAM-D), brief psychiatric rating scale (BPRS), and Unified Parkinson's disease rating scale (UPDRS) were administered to clinically probable non-demented patients with SND-type MSA and patients with IPD matched for age and motor disability, at baseline and after receiving levodopa. At baseline total HAM-D score was greater in patients with IPD. Overall, BPRS score did not differ between the two groups; however, patients with IPD scored higher on anxiety items of the BPRS, and patients with MSA had higher scores on the item indicating blunted affect. After levodopa, both groups improved significantly in UPDRS and HAM-D total scores (just significant for patients with MSA). Patients with IPD improved significantly in total BPRS score but patients with MSA did not. At baseline patients with IPD were more depressed and anxious than patients with MSA who, by contrast, showed blunted affect. After levodopa, depression and anxiety of patients with IPD improved significantly whereas the affective detachment of patients with MSA did not change. Major neuronal loss in the caudate and ventral striatum, which are part of the lateral orbitofrontal and limbic circuits, may be responsible for the blunted affect not responsive to levodopa therapy found in patients with MSA.

Cognitive dysfunction and impaired organization of complex motility in degenerative parkinsonian syndromes.

BACKGROUND: A frontostriatal pattern of cognitive decline, consisting of a frontal lobe-like syndrome without genuine cortical defects such as amnesia, apraxia, aphasia, or agnosia, is well established in basal ganglial diseases. Recent pathological investigations, however, have again noted cortical damage in progressive supranuclear palsy (PSP), suggesting that cortical defects could be present. OBJECTIVES: To delineate the pattern of cognitive impairment and to detect higher-order motor impairments (including ideomotor apraxia) in parkinsonian syndromes. PATIENTS AND METHODS: We assessed ideomotor apraxia, and simple and sequential tapping in patients with Parkinson disease, multiple system atrophy, and PSP with similar disease severity, age range, and education. We also administered a comprehensive battery of neuropsychological tests to examine general intelligence, memory, executive functions, attention, and visuospatial orientation. The results were compared between groups and with a matched normal control group. RESULTS: Sequential tapping and the imitation of sequences of gestures were impaired in all patient groups, with patients with PSP performing worse than the other groups. Based on ideomotor apraxia scores and a qualitative analysis of errors, 3 patients with PSP and 2 with multiple system atrophy were considered apraxic. General intelligence and executive functions were compromised in all patient groups. The impairment of patients with PSP was more pervasive than that of the other groups, and included compromise of visuospatial functions, attention, and memory. Discriminant analysis of all cognitive and motor tests showed that the tapping and ideomotor apraxia tests best identified the patients vs control subjects. CONCLUSIONS: The presence of cortical as well as subcortical damage in patients with PSP and those with multiple system atrophy is indicated by the presence of pervasive cognitive and motor disturbances in the former, substantial motor disorganization in the latter, and the finding of ideomotor apraxia in some patients with these diseases. Furthermore, the discovery that tests of motor and gesture best identified all patients vs control subjects is consistent with the existence of a common motor disorganization in these parkinsonian syndromes, in agreement with the known damage to the corticostriatal pathways in these conditions.

Variations in axial, proximal, and distal motor response to L-dopa in multisystem atrophy and Parkinson's disease.

The purpose of this study was to quantitatively compare the motor response to L-dopa in Parkinson's disease (PD) and striatonigral-type multisystem atrophy (MSA) patients. Ten consecutive MSA patients were compared with nine PD patients selected to have similar overall motor compromise, age, and mental state. The performance of simple repetitive axial movements plus bilateral proximal and distal limb movements; overall motor response assessed by the Unified Parkinson Disease Rating Scale (UPDRS); as well as scores from the UPDRS items evaluating speech/facial expression, postural stability, and posture/gait were assessed 90 min and 12 h (baseline) after L-dopa administration. The total UPDRS score, all subcategory scores, and all body movements improved significantly in the PD group. Proximal and distal limb akinesias and speech/facial expression improved in some MSA patients. Lack of response of axial akinesia to L-dopa in MSA correlates with a presumed greater loss of postsynaptic dopaminergic receptors in the dorsolateral putamen, while improvement in distal and proximal limb muscle akinesias in MSA patients may be related to relative preservation of the ventral putamen.

Cabergoline in Parkinson's disease complicated by motor fluctuations.

Cabergoline is a long-acting D2 dopamine (DA) agonist. We conducted an open study to investigate the effectiveness and tolerability of cabergoline, administered once a day orally, in 50 consecutive patients with Parkinson's disease complicated by motor fluctuations and dyskinesias. In 15 patients cabergoline replaced another direct DA agonist. Evaluation after 6 months of treatment (also including patients who dropped out during this period), showed an improvement in off or on hours, or both, in excess of 50% in 27 patients, comprising 20 of the 35 patients (57%) previously untreated with DA agonists and seven of the 15 patients (47%) already on DA agonists when the study began. Of the 22 patients who received the treatment for 1 year, the improvement was maintained up to final evaluation in the patients not on DA agonists at admission (n = 16), whereas a slight deterioration in clinical condition was observed in the patients already on DA agonists at admission (n = 6). Only six patients showed a detectable increase in dyskinesias. The most common side effects were gastric upset (n = 12), orthostatic hypotension (n = 3), and ankle edema (n = 3), all mild; also observed were two cases of pleural effusion/pulmonary fibrosis. Twenty patients (40%) failed to complete the treatment; of these, five (10% of total) dropped out because of adverse effects. It is concluded that once-daily administrations of cabergoline are useful for treating patients with Parkinson's disease with motor fluctuations and may advantageously substitute other DA agonists. The side effects of the drug are generally mild, although two cases involving pleuropulmonary complications did emerge.

Progression of motor and cognitive impairment in Parkinson's disease.

We performed a longitudinal study (mean follow-up 86.7 months) to evaluate motor and mental deterioration in patients with Parkinson's disease. Of the original 91 patients, only 61 could be re-examined 7 years later and 11 of these had become demented (PD-Dems). PD-Dems were older with worse motor and, obviously, cognitive performance than non-demented parkinsonian patients (PDs). A global cognitive decay index (DI) was calculated for each patient. Based on this, non-demented PDs were further split into 38 stable parkinsonian patients (S-PDs) with DI-30% to +30%, and 10 deteriorated but non-demented parkinsonian patients (D-PDs) with a DI worse than -30% (as had PD-Dems). D-PDs were older and had greater motor impairment than S-PDs but did not differ from PD-Dems on these measures. D-PDs and PD-Dems deteriorated especially in attention, visuospatial and executive ability tests. Ageing seems to be the main predictive factor for mental deterioration.

Decreased CSF levels of homovanillic acid in ALS patients.

Levels of homovanillic acid (MVA) were measured in lumbar cerebrospinal fluid from 24 patients affected by amyotrophic lateral sclerosis (ALS) and compared with those found in 11 patients with Parkinson's disease (PD) and 10 patients with lumbar disc herniations who served as controls. Mean HVA levels were significantly decreased in ALS and PD patients. These findings are consistent with impairment of central dopaminergic systems in ALS as well as suggesting degeneration of neuroanatomical structures other than motor neurons.

MRI in corticobasal degeneration.

Corticobasal degeneration is a degenerative disease characterized by asymmetric brain atrophy and clinically by asymmetric onset of an akinetic-rigid syndrome with apraxia, dysarthria and dysphagia. Diagnosis must be confirmed by autopsy. We have investigated the ability of MRI to detect asymmetric atrophy to support the clinical diagnosis and permit differential diagnosis against other degenerative disorders. Ten patients with clinical suspicion of corticobasal degeneration were studied by brain MRI, and the images were reviewed with the side of greater clinical involvement unknown to the reviewer. The original reports of MR scans were also reviewed. MRI demonstrates that cortical atrophy is asymmetric and more marked in the posterior frontal and mainly in the parietal regions on the side contralateral to the clinical symptoms. Asymmetry was rarely detected on the first reading. Our review of MRI findings demonstrates that it is possible to detect asymmetrical parietal atrophy, thus supporting the clinical diagnosis of corticobasal degeneration. It is essential to be aware of the disease and alert for asymmetries in order to discern the more involved side. No abnormalities were detected in the basal ganglia.

Sneddon's syndrome: clinical and immunohistochemical findings.

Results of immunological studies on skin biopsies of 5 patients with Sneddon's syndrome are reported. Also studied were coagulation factors and autoantibodies believed to play a role in this syndrome. Hemostasis was normal except for a mild increase of fibrinogen in one subject; lupus anticoagulant (LAC) and anticardiolipin antibodies were negative in all. The skin biopsies ruled out systemic vasculitis and vasculitis in association with connective tissue diseases. Sneddon's syndrome is a peculiar clinicopathological condition, probably with several etiologies, but is distinct from primary antiphospholipid syndrome.

Multiple system atrophy. Clinical and MR observations on 42 cases.

Probable or possible multiple system atrophy (MSA) was diagnosed on strict clinical criteria in 42 patients: 20 with combined parkinsonism and cerebellar ataxia, 9 with striatonigral degeneration (SND) and 13 with olivopontocerebellar atrophy (OPCA). All patients were then studied with 0.5 and/or 1.5 Tesla magnetic resonance (MR) units. MR imaged putaminal abnormalities in all 9 patients with SND and posterior fossa abnormalities consistent with OPCA in all 13 patients with this diagnosis. Of the 20 patients with parkinsonism and cerebellar involvement, classified as probable MSA, 7 presented putaminal abnormalities only, 3 abnormalities consistent with OPCA only and 10 a combination of both. These findings show strong MRI support for the clinical diagnosis of MSA.

Response to L-DOPA in multiple system atrophy.

A poor response to L-DOPA in addition to parkinsonian, cerebellar, and autonomic signs is commonly regarded as indicative of clinical multiple system atrophy (MSA). We compared the motor response to a single oral administration of 250 mg L-DOPA/25 mg carbidopa in eight MSA patients and eight Parkinson's disease (PD) patients with the "on-off" phenomenon, evaluating L-DOPA peripheral pharmacokinetics. Motor response was consistently good in all PD patients, but only four MSA patients had a (moderate) response. Pharmacokinetic parameters did not differ between the groups. The varying extent of putaminal damage could be responsible for the differing motor response to L-DOPA in MSA patients.

Cognitive and motor performance in multiple system atrophy and Parkinson's disease compared.

Nineteen patients with multiple system atrophy (MSA) of striato-nigral degeneration type were tested to examine cognitive and motor performance. Parkinson's disease (PD) patients and healthy subjects served as controls. The MSA and PD patients showed similar cognitive dysfunction and motor impairment, performing poorly in the visuo-spatial organization, the construction tests and motor assessment tests. Movement times were much longer in MSA than PD patients. The association of nigral with putaminal damage may explain the more severe bradykinesia in MSA.

Sneddon's syndrome and renal carcinoma. Case report.

A patient with Sneddon's syndrome in association with renal neoplasm is discussed. The association has not been reported before and raises questions concerning the pathogenesis of vascular proliferation in Sneddon's syndrome.

Chronic treatment with L-threonine in amyotrophic lateral sclerosis: a pilot study.

Thirty patients suffering from amyotrophic lateral sclerosis were included in an open therapeutical trial. They were randomized to receive either L-threonine (Thr), a precursor of the inhibitory amino acid glycine, or vitamin B or carnitine. Thirteen patients (9 patients on Thr and 4 control subjects) completed the 1-year trial. No statistical differences were observed between the treated group and the control patients in the decline of the clinical assessment score. Nevertheless, Thr-treated patients complained less frequently of respiratory failure than the control group despite bulbar involvement being more common in the Thr group at entry.