Qualitative evaluation of the Rey-Osterrieth Complex Figure Test in patients with progressive supranuclear palsy.

Objective: In early stages of disease, the differential diagnosis between Parkinson's Disease (PD) and atypical parkinsonism, such as Progressive Supranuclear Palsy (PSP), could be challenging. Growing attention has recently been dedicated to investigating neuropsychological markers of degenerative parkinsonism. The Rey-Osterrieth Complex Figure Test (ROCFT) copy score was hypothesized able to differentiate PSP from PD. However, ROCFT is a drawing test requiring multiple cognitive abilities and it is still unknown which of them assumes an important role in PSP performance. Using a qualitative scoring system, we investigated which cognitive abilities underpin the PSP performance at the ROCFT copy trial. Moreover, we evaluated usefulness of the BQSS scores in discriminating PSP from PD. Methods: Thirty PSP-Richardson's Syndrome (PSP-RS) patients, 30 PD patients, and 30 healthy control (HC) comparable for age, education, and gender were enrolled. All subjects underwent a neuropsychological evaluation; ROCFT copy were evaluated with the 36-Point Score and with the Boston Qualitative Scoring System (BQSS). Results: PSP-RS patients performed worse in ROCFT 36-Point Score and in several BQSS scores compared to other groups. Most suitable scores discriminating PSP-RS from PD were "Perseveration" and "Vertical Expansion" of BQSS. A logistic regression model considering "Perseveration" and "Vertical Expansion" showed a diagnostic accuracy of 83,3% for PSP-RS condition. Conclusion: our findings showed that "Perseveration" and "Vertical Expansion" BQSS scores were useful in discriminating PSP-RS from PD. "Perseveration" and "Vertical Expansion" BQSS scores might be included in the cognitive evaluation along with quantitative scores when PSP diagnosis is considered.

Association Between CSF Beta-Amyloid and Apathy in Early-Stage Alzheimer Disease.

AIM: The apathetic syndrome is a common clinical feature in patients with Alzheimer diseases (AD), from preclinical phases to late stages of dementia, and it is strongly related to major disease outcomes. Unfortunately, no specific pharmacological treatments for apathy have been accomplished so far. Translational evidences have previously shown that a link between apathy and hallmarks of AD-related pathophysiology, that is, ß-amyloid (Aß) plaques and neurofibrillary tangles, exists. However, only few studies investigated the association between core biomarkers of AD and apathy scores, finding conflicting results. METHODS: Thirty-seven patients were identified as having AD dementia according to National Institute on Aging-Alzheimer Association 2011 criteria. All participants underwent an extensive diagnostic workup including cerebrospinal fluid (CSF) assessment to measure the concentrations of Aß42, t-tau, and pTau181. To follow, they were stratified as: apathy absence, apathy mild, and apathy severe according to the Neuro Psychiatric Inventory-apathy item scores. We investigated for potential associations between apathy scores and CSF biomarkers concentrations as well as for differences in terms of clinical and CSF biomarkers data across the 3 apathy groups. RESULTS: The CSF Aß42 concentrations were negatively correlated with apathy scores. In addition, patients with severe apathy had significantly lower Aß42 levels compared to nonapathetic ones. CONCLUSION: Based on our results, we encourage further studies to untangle the potential association between the complex pathophysiological dynamics of AD and apathy which may represent an innovative reliable clinical outcome measure to use in clinical trials, investigating treatments with either a symptomatic or a disease-modifying effect.

Mild affective symptoms in de novo Parkinson's disease patients: relationship with dopaminergic dysfunction.

BACKGROUND AND PURPOSE: The investigation of the relationship between affective symptoms and dopamine transporter (DAT) density provided conflicting data in both Parkinson's disease (PD) and non-PD patients. However, the potential interference of psychoactive as well as anti-parkinsonian drugs on DAT density should be taken into account. OBJECTIVE: To investigate the relationship between affective symptoms and pre-synaptic dopaminergic function in de novo PD patients. METHODS: Forty-four de novo PD consecutive outpatients were recruited, and the severity of anxious symptoms was evaluated with the Hamilton Anxiety Rating Scale (HAM-A), the severity of depressive symptoms with the Hamilton Depression Scale (HAM-D) and the Beck Depression Inventory (BDI). Six patients had a formal diagnosis of depression. All patients performed (123) I-FP-CIT SPECT, and semi-quantitative striatal indices were calculated. RESULTS: Disease severity, as measured by Unified Parkinson's Disease Rating Scale (UPDRSIII), was inversely correlated with bilateral striatal indices. Bilateral striatal uptake was significantly positively correlated with HAM-D (r.329; r.423, respectively, right and left), BDI (r.377; r.360, respectively, right and left) and HAM-A (r.338; r.340, respectively, right and left). After controlling for age, disease duration and severity, and Mini Mental State Examination (MMSE), no significant reduction in r-values was observed (P < 0.05). CONCLUSION: Our data support the existence of a relationship between depressive and anxious symptoms and the striatal (123) I-FP-CIT uptake. The finding of an increased DAT density associated with mild affective symptoms could be due to the lack of compensatory mechanisms usually present in early PD, and/or it might have a pathogenic role in affective symptoms by reducing the dopaminergic tone in the synaptic cleft.

Sleep disturbances in elderly subjects: an epidemiological survey in an Italian district.

OBJECTIVES: Disturbed sleep is common in elderly people and has been related to comorbidities. The aim of this study was to evaluate the prevalence of sleep problems and their relationship with chronic disease in an elderly population. MATERIALS AND METHODS: The whole population of subjects aged more than 65 years, in the municipality of Vecchiano, Pisa was considered as eligible and underwent a clinical interview and a questionnaire about insomnia, sleepiness, snoring and sleep apnea. A model of logistic regression was applied to the data. RESULTS: The participation rate was 60.3% (1427 subjects). Insomnia was observed in 44.2% of our population, while sleepiness in 31.3%, snoring in 47.2% and sleep apnea in 9.0%. The most common diseases associated with sleep symptoms were depression, cognitive decline and diabetes. CONCLUSIONS: Our results confirm that sleep problems are very common in elderly subjects and closely related to medical and psychiatric illnesses.

Results by motor cortex stimulation in treatment of focal dystonia, Parkinson's disease and post-ictal spasticity. The experience of the Italian Study Group of the Italian Neurosurgical Society.

Extradural motor cortex stimulation has been employed in cases of Parkinson's disease (PD), fixed dystonia (FD) and spastic hemiparesis (SH) following cerebral stroke. Symptoms of PD are improved by EMCS: results were evaluated on the basis of the UPDRS and statistically analysed. In PD EMCS is less efficacious than bilateral subthalamic nucleus (STN) stimulation, but it may be safely employed in patients not eligible for deep brain stimulation (DBS). The most rewarding effect is the improvement, in severely affected patients, of posture and gait. FD, unresponsive to bilateral pallidal stimulation, has been relieved by EDMS. In SH reduction of spasticiy by EMCS allows improvement of the motor function.

Trigeminal neuralgia. Non-invasive techniques versus microvascular decompression. It is really available any further improvement?

Analysis of the results of the various methods for treatment of typical trigeminal neuralgia (TN) based on the literature and personal experience. The personal experience includes 847 cases: total thyzotomy in the posterior fossa 17 cases; rhyzotomy in the posterior fossa sparing the intermediate fibers 16 cases; microvascular decompression (MVD) 141 cases; controlled thermorhizotomy (PTR) 54 cases; Fogarty Balloon compression (FBC) 223 cases; glycerol ganglyolis (PGG) 12 cases; miscellaneous 48 case; medical treatment only 310 cases; cyberknife radiosurgery (CKR) 46 cases. The follow-up in this series is 1-32 years. MVD of the Vth cranial nerve in posterior fossa gives the best results in term of long-term pain relief without collateral effects in drug-resistant TN. Percutaneous techniques (PTR, PGG, FBC) are indicated in patients either without neurovascular conflict or with excessive surgical risk. Stereotactic radiosurgery (SRS) and CKR might be considered an improvement of percutaneous and surgical techniques, but contrary to the expectations, the rate of complete pain relief at long term is lower. SRS and CKR are less effective than MVD which, in spite of the risks it entails, remains the choice treatment for typical trigeminal neuralgia.

Posttraumatic epilepsy with special emphasis on prophylaxis and prevention.

Posttraumatic epileptic seizures have an incidence of about 10% in series of severe head injuries. Control of "early seizures", i.e. those occurring in the first week after injury, is mandatory. Attacks, especially if recurrent, may add secondary damage to the injured brain: intravenous phenythoin with therapeutic plasma level allows control of the attacks. Seizures occurring months or years after injury are called "late seizures": recurring "late seizures" make up the clinical syndrome of "posttraumatic epilepsy". "Prophylaxis" should mean that drug treatment, given for a more or less prolonged period of time, blocks permanently the ripening of the epileptogenic foci avoiding the occurrence of seizures. In animal "prophylaxis" by antiepileptic drugs seems efficacious in many experimental models including iron induced epilepsy which is considered a model of posttraumatic epilepsy and vice versa. In the human being "prophylaxis" has been attempted with: phenytoin, phenobarbital, carbamazepine, valproate but without success. During treatment period the occurrence of seizures is prevented but, after discontinuation of the drug, seizures occur just as in non treated patients. The ripening of the epileptic focus in posttraumatic epilepsy, as in iron induced epilepsy, seems to be due to a cascade of events beginning with haemorrhage, haemolysis, iron or heme compound liberation, free radical formation, peroxidation and cell death. Experimentally free radical scavengers and antiperoxidants have marked prophylactic effect. Some of them (phosphate diester of vitamin E and C, melatonin, vanillyl alcohol) may be employed in clinical practice, but up to date there is no controlled study in human beings.

Extradural motor cortex stimulation (EMCS) for Parkinson's disease. History and first results by the study group of the Italian neurosurgical society.

The preliminary results obtained by the Study Group for Treatment of Involuntary Movements by Extradural Motor Cortex Stimulation (EMCS) of the Italian Neurosurgical Society, are reported. The series includes 16 cases of very advanced Parkinson's Disease (PD), aged 46-81; 15 of them were not eligible for Deep Brain Stimulation. Ten cases have been evaluated at 3-30 months after implantation. Unilateral, sub-threshold extradural motor cortex stimulation (2 8 Volt, 100-400 microsec., 20-120 Hz) by chronically implanted electrodes, relieves, at least partially, but sometime dramatically, the whole spectrum of symptoms of advanced PD. Tremor and rigor bilaterally in all limbs and akinesia are reduced. Standing, gait, motor performance, speech and swallowing are improved. Benefit is marked as far as axial symptoms is concerned. Also the symptoms of Long Term Dopa Syndrome -dyskinesias, motor fluctuations - and other secondary effect of levodopa administration psychiatric symptoms - are improved. Levodopa dosage may be reduced by 50%. The effect seems persistent and does not fade away with time. Improvement ranged, on the basis of the UPDRS scale, from <25% to 75%. There was only one case of complete failure. Quality of life is markedly improved in patients who were absolutely incapable of walking and unable arise out of chair. After stimulation they could walk, even if assistance was necessary. Improvement was observed also in those with disabling motor fluctuation and dyskinesias which could be abolished.

Further experience with extradural motor cortex stimulation for treatment of advanced Parkinson's disease. Report of 3 new cases.

AIM: To report the results obtained with the extradural motor cortex stimulation in Parkinson's disease. METHODS: Three patients were submitted to MRI images and functional MRI in order to identify the upper limb motor area. Then a quadripolar electrostimulator was introduced in the extradural space, through 2 burr holes. RESULTS: Unilateral, extradural motor cortex stimulation relieves, at least partially, but sometime dramatically, the whole spectrum of symptoms in advanced Parkinson disease: tremor and rigor bilaterally in all limbs; akinesia; standing, anteropulsion, gait; motor performance; dysphagia; speech and swallowing. Also the symptoms of long term dopa syndrome--dyskinesias, and other secondary effect of L-dopa administration, psychiatric symptoms--are improved. CONCLUSION: The results seems do not fade away with time. Drug dosage may be reduced by 50%. We suggest early employ of transdural motor cortex stimulation.

Spinal meningioma during hydroxyurea therapy. A paradoxycal case report.

We report the case of a 65-year-old woman who developed symptoms of spinal cord compression due to a spinal meningioma after 10 years of treatment with hydroxyurea (1000 mg/day) for essential thrombocytemia. This case provides a paradigm for the occurrence of symptomatic meningioma in course of HU therapy.

The important role of pain in neurorehabilitation. The neurosurgeon's approach or (neurorehabilitation: the neurosurgeon's role with special emphasis on pain and spasticity).

Pain syndromes due to peripheral or central nervous system damage, or both, may hinder neurorehabilitation. Control of pain may be obtained by ablative or augmentative procedures. Of the ablative modes only DREZ and Cordectomy are still being employed in cases of pain due to Brachial Plexus Avulsion and conus and cauda damage at T9-L1: in both pain is not simply due to "deafferentiation". The augmentative procedures include spinal cord, deep brain and cortical stimulation. Subarachnoid infusion of drugs (midazolam, clonidine, baclofen, etc.) is a new avenue open to control pain. Indications, results and mechanisms of action of those procedures in neuropathic pain are discussed on the basis of literature and personal experience.

Nitric oxide synthase and cytochrome c oxidase changes in the tumoural and peritumoural cerebral cortex.

BACKGROUND: We analysed changes in nitric oxide synthase (NOS) and cytochrome oxidase (CO) activities in the tumoural and peritumoural cerebral cortex in order to investigate: a) the role of NO in tumourigenesis, in TBF regulation, and in vasogenetic PBE; b) the metabolic changes caused by the neoplasm in the surrounding tissues. METHOD: Intra-operative samples of cerebral cortex were studied by means of immunohistochemistry for nNOS and iNOS, and by histochemistry for NADPH-diaphorase (NADPH-d) and CO. FINDINGS: In contrast with normal cortex, reactive glial cells and the endothelium of small blood vessels displayed strong NADPH-d and iNOS activities in oedematous peritumoural tissue. In the tumoural cortex, NADPH-d and nNOS-positive neurones were reduced in number and their dendrites were thin and interrupted, and infiltrates of NADPH-d and iNOS-positive tumoural cells were frequent. CO activity was decreased in the deep layers of peritumoural cortex, and it was almost absent in the tumoural cortex. INTERPRETATION: In peritumoural and tumoural cortex changes in NOS and CO activities suggest that the coupling between neuronal activity and blood flow is impaired in the damaged cerebral cortex, and that the increase in NOS activity may play a role in tumour vascularization and progression.

Sudden presentation of intracranial meningioma after elective general anesthesia.

A case of "silent" intracranial meningioma unmasked by narcosis is described. The diagnosis was made because of the patient's failure to wake up after elective general anesthesia for orthopaedic surgery. Factors leading to this complication and its management are discussed. Early computed tomography scan and antiedema therapy are strongly suggested for these patients.

Neuropsychological and neurophysiological evaluation after anterior communicating artery (ACoA) aneurysm surgery.

BACKGROUND: We evaluated high cerebral functions 6 months after surgery for bleeding ACoA aneurysms comparing neurophysiological and neuropsycological tests. METHODS: Twelve patients were chosen among a series of cases operated on in the first 48 hours after ACoA aneurysm bleeding. All of them were in Hunt-Hess grade I or II. We excluded patients over 65 years, or with intracranial haematomas, intraventricular haemorrhage, hydrocephalus, or with multiple or giant aneurysms. All of them underwent neurophysiological evaluation with recording and mapping of long latency (P300) auditory and visual event-related potentials (ERPs) and a neuropsychological assessment for memory, intelligence, frontal lobe functions and language. RESULTS: Neuropsychological assessment: All patients were severely damaged on phonemic fluency. In a first group (group A: 3 cases) tests were all in a normal range. In a second (group B: 3 cases) the tests showed severe impairment on learning and long term memory. In a third (group C: 6 cases) tests showed memory and "frontal lobe" deficits. Neurophysiological assessment: The whole group of patients showed significant delay in ERPs recordings compared to controls. ERPs of patients in group A and B showed no significant differences from controls, while being significantly delayed in 5 patients out of 6 of group C. CONCLUSIONS: All patients had difficulties in the phonemic task in which a notable cognitive effort is necessary, while intelligence, short term memory, attention and language were within normal limits. Patients in group C showed severe frontal lobe type cognitive impairment. Those ones in groups A and B did not present cognitive derangements (A) or only memory and learning impairment (B). ERPs may be an objective parameter in the follow-up of cases with cognitive impairment, even if neurophysiological tests cannot be replaced.

Peri- and postoperative pain valutation in carpal tunnel release of median nerve compression.

We analysed 108 patients, operated on day surgery, for carpal tunnel release of median nerve compression, to evaluate peri- and postoperative pain. We made in all cases a short intertenarian incision (25 mm) with microsurgical technique and local anaesthesia using mepivacaine 2% without vasoconstrictor. We evaluated pain for local anaesthetic infiltration as VRS (Verbal Rating Scale) 6,3 median-time to the first possible analgesic assumption (in all cases paracetamol 500 mg), total analgesic assumption, pressure algometry (to evaluate "allodiny") after the first 48 hours and subjective pain intensity by a numerical pain scale. Pain intensity on first drug assumption (after a mean time of 7 hours from the end of surgery) had a mean VAS value of 2,15; while after a second assumption of analgesic (after a mean time of 15 hours from surgery) had a mean VAS value of 2. Mean total analgesic assumption was 1,64 tablets of paracetamol 500 mg. From these data we may deduce that peri- and postoperative pain following median nerve decompression with this technique and anaesthesia, has a moderate intense peak of brief duration, for local anaesthetic infiltration (that seems to be the most painful event) and modest and not constant pain in the postoperative time (more evident 7 and 15 hours from the end of surgery). It may be useful association with mepivacaine bicarbonate solutions or injecting less painful local anaesthetic.

De novo cavernoma case report and review of literature.

BACKGROUND: De novo cavernoma, reported with the familial form of disease, is rare in cases with a negative family history. Cranial radiation, coexistent vascular malformation, genetic and hormonal factors, previous surgery for intracranial lesions, or other apparently unrelated intracranial lesions have been reported as risk factors. METHODS: We report a case of de novo cavernoma without a family history and without previous irradiation or any other known risk factors. The genesis of this lesion is discussed. RESULTS: To our knowledge, this is the first case, based on two separate magnetic resonance imaging (MRI) studies, demonstrating evidence of de novo cavernous malformations in the absence of familial history, brain radiation therapy, or other apparently unrelated intracranial tissue lesions. Based on previous negative computed tomography scans, other cases have been presented as de novo cavernous angiomas; thus it is possible that the newly discovered cavernoma existed previously but had been missed on previous poorer quality or lower resolution imaging studies. CONCLUSIONS: Cavernoma can arise even without an associat family history; in our case, a previous head injury could have set off either a genetic cascade with attendant endothelial proliferation or a latent virus.

[Therapeutic decisions and grading of subarachnoid hemorrhage]. / Scelte terapeutiche e grading nell'ESA.

Early admission and medical treatment can improve prognosis in patients with subarachnoid hemorrhage (SAH). In our Centre in 10 years, 595 patients with SAH have been treated: 422 were admitted within 24 hours (71%) and 498 (84%) within 72 hours. 374 underwent surgical treatment: 283 within 48 hours and 91 underwent late surgery. Thirty-three patients underwent emergency surgery for intracranial hematomas, with a mortality rate of 30%. One hundred eighty-one patients in Hunt-Hess grade I-II underwent early surgery. Mortality rate was 7%. Mortality rate for rebleeding, when surgery was delayed was more than 10%. Patients in Hunt-Hess grade III underwent early surgery in the majority of cases (68 out of 111). Only in 52% of cases surgical result was good. Thirty-four out of 108 in grade IV-V underwent early surgery, with a mortality rate of 45%. The analysis of general results shows that early surgery improves prognosis in Hunt-Hess grade III patients. Also patients in Hunt-Hess grade III-IV-V can take advantage of early surgery. Old age, arterial hypertension and angiographical vasospasm do not worsen prognosis even in patients operated on early. Endovascular treatment even in acute phase has improved results especially in cases of certain aneurysms types such as posterior circulation aneurysms.

[Pharmacologic therapy of subarachnoid hemorrhage]. / Terapia farmacologica dell'emorragia subaracnoidea.

Medical treatment of subarachnoid haemorrhage, is focused on the prevention of rebleeding and vasospasm, of damages of oxitading products, and on the improvement of general conditions of the patient. Some authors consider use of antifibrinolytic usefull to reduce the risk of rebleeding, but the percentage of hydrocephalus and ischemia are increased. In our Centre combination of nimodipine-cloricromene and hemodilution is used for the prevention of vasospasm. We report conclusions about 216 patients in I-II-III grade of Hunt-Hess scale, treated before 48 hours from SAH. We obtained only 8% postspasm ischemias, with no neurological deficit, and only 23% of increased cerebral blood flow revealed by transcranial Doppler. Cloricromene is used only after aneurysm is occlused. It presents different action mechanisms. It is an inhibitor of platelet activation and aggregation, of cyclooxygenase and lipooxygenase activity, so reducing thromboxanes ratio. Phospholipase A2 inhibition it's possible but not demonstrated. It also interferes with phosphoinositoles path and so with proteinkinase C activity, and reduces hemostatic thrombotic balance activation and leukocyte endothelial adhesion and activation. It reduces, finally, the release of free radicals, cytokines inflammation amplyfing. The reduced damage to the endothelium allows the releasing of vasodilatatory agents like NO.