Multiple cycles of PBPC-supported high-dose carboplatin and paclitaxel following mobilization with epirubicin and cisplatin are feasible but ineffective in treating patients with advanced non-small cell lung cancer.

We verified the feasibility of a multi-cycle peripheral blood progenitor cell (PBPC)-supported high-dose chemotherapy (HDC) regimen in patients with non-small cell lung cancer (NSCLC). The HDC regimen consisted of a single course of high-dose epirubicin given in combination with cisplatin plus filgrastim, followed by three courses of high doses of carboplatin and paclitaxel with PBPC reinfusion and filgrastim. Of the 16 enrolled patients, 13 provided an adequate number of PBPCs by a single leukapheresis, while in the three needed two procedures, with a median number of CD34+, CD34+/CD33- and CD34+/CD38- cells collected per patient was 13.5 x 10(6), 10.9 x 10(6) and 0.9 x 10(6)/kg, respectively. No toxic death occurred, and the collected PBPCs supported a rapid hematopoietic reconstitution after HDC; however, seven patients early interrupted the treatment early due to early progressive disease (n=4) or prolonged grade 3 peripheral neurotoxicity (n=3). Despite an overall response rate of 42%, the median survival for stage IV patients has been 5 months (range: 1-25+). Of two patients with stage IIIB NSCLC, one is continuously disease-free at 71+ months, while of 14 with stage IV disease, one is currently alive with disease at 25+ months. In conclusion, the combination of high-dose epirubicin with cisplatin plus filgrastim is an effective regimen in releasing large amounts of PBPCs, which can then be safely employed to support multiple courses of HDC. Multiple cycles of PBPC-supported high-dose carboplatin and paclitaxel are ineffective in treating patients with advanced NSCLC.

Corticosteroids or ACTH for acute exacerbations in multiple sclerosis.

BACKGROUND: Corticosteroids are often used to improve the rate of recovery from acute exacerbation in multiple sclerosis (MS) patients. However, it is still unclear just how relatively effective these agents are and the type of drug, optimal dose, frequency, duration of treatment and route of administration are unknown. OBJECTIVES: The object of this review was to determine the efficacy and safety of corticosteroids or ACTH in reducing the short and long term morbidity from MS. Moreover, we wished to examine from indirect comparisons if the effect of corticosteroids is different according to different doses and drugs, routes of administration, length of treatment. SEARCH STRATEGY: A search strategy developed for the Cochrane MS Group (last searched: June 1999) completed with handsearching and personal contacts with trialists and pharmaceutical companies was used. SELECTION CRITERIA: All randomised, double-blind, unconfounded trials comparing corticosteroids or ACTH to placebo in patients with MS, treated for acute exacerbations, without any age or severity restrictions, were evaluated. DATA COLLECTION AND ANALYSIS: Two reviewers independently selected articles for inclusion, assessed trials' quality and extracted the data. A third reviewer cross-checked them and disagreements were resolved by a joint discussion. MAIN RESULTS: Six trials contributed to this review; a total of 377 participants (199 treatment, 178 placebo) were randomised. The drugs analysed were methylprednisolone (MP) (four trials, 140 patients) and ACTH (two trials, 237 patients). Overall, MP or ACTH showed a protective effect against the disease getting worse or stable within the first five weeks of treatment (odds ratio[OR]=0.37, 95% confidence interval [CI] 0.24-0.57) with some but non significant greater effect for MP and intravenous administration. Short (five days) or long (15 days) duration of treatment with MP did not show any significant difference. Only one study (with 51 patients) reported data after one year of follow-up: no difference between oral MP and placebo in the prevention of new exacerbations or improvement in long term disability was detected. No data are available beyond one year of follow-up to indicate whether steroids or ACTH have any effect on long-term progression. One study reported that a short term treatment with high dose intravenous MP was not attended by adverse events. On the contrary, gastrointestinal symptoms and psychic disorders were significantly more common in the oral, high-dose MP than in the placebo group. Weight gain and edema were significantly more frequent in the ACTH group than in controls. REVIEWER'S CONCLUSIONS: We found evidence favouring the corticosteroid MP for acute exacerbation in MS patients. Data are insufficient to reliably estimate effect of corticosteroids on prevention of new exacerbations and reduction of long-term disability. Studies assessing long term risk/benefit and adverse effects of corticosteroids in MS patients are urgently needed.

[The correlation between the type of positivity of the tilt test and a simultaneous electroencephalogram: the preliminary results]. / Correlazione tra tipo di positività del tilt test ed elettroencefalogramma simultaneo: risultati preliminari.

BACKGROUND: Today the first-choice examination to study neurally-mediated syncope is the tilt test. There are still many aspects to be clarified on the pathophysiology of neurally-mediated syncope, and much uncertainty remains on the therapeutic procedure to adopt. Recent research has investigated the role of neurohumoral agents, thus shifting interest to the pathogenetic role of the central nervous system, over and above that of the already widely studied vegetative nervous system. This is why we decided to carry out the tilt test with simultaneous electroencephalogram (EEG) recordings, with the aim of documenting any possible correlation between test positivity, according to Sutton's classification, and the EEG results. METHODS: We studied 15 patients (8 males, 7 females, age range 18-74 years) with a history of repeated syncopal and presyncopal episodes who had formerly undergone numerous clinical and instrumental examinations, including EEG, with negative results. The tilt test was carried out with continuous measurement of blood pressure (Ohmeda Finapres System) and simultaneous EEG recording. RESULTS: Ten patients (66%) were positive, 6 had experienced syncope episodes (4 type 2A and 2 type 1) and 4 presyncope (1 type 2A and 3 type 1). In all the syncope positive patients the EEG showed modifications in comparison with basal EEG, whereas only 50% of the presyncope positive patients showed slight alterations. There was no EEG alteration for tilt negative patients. The EEG result was markedly different in patients with tilt-induced type 2A syncope in comparison with those with type 1. Type 2A showed the following: 1) slowdown and reduced amplitude of electrical activity during the prodromes; 2) during the syncope, first pseudorhythmic then polymorphic delta activity were followed by total disappearance of activity ("flat" EEG); 3) then, in inverse sequence, reappearance of polymorphic then pseudorhythmic delta activity (average duration of syncope 37 s); 4) lastly, slowdown and reduced amplitude of electrical activity similar to that preceding the syncope. Whereas type 1 revealed: 1) no alteration of electrical activity during the prodromes; 2) during the syncope, first theta then polymorphic delta activity (average duration of syncope 16 s); 3) subsequent normal EEG. CONCLUSIONS: These observations indicate a correlation between the type of tilt test positivity and the EEG results, the latter being markedly more serious in type 2A than in type 1. EEG behavior, different in the two types also during the prodromes and the post-syncopal phase, would suggest a cerebral circle vasoconstriction mechanism in type 2A but not in type 1 mixed with a prevalent vasodepressive component. Should these preliminary results be confirmed by further data there will be evident clinical, prognostic and therapeutic implications. In the light of the considerably different involvement of the central nervous system, we believe it will be necessary to redefine the various types of neurally-mediated syncope in terms of seriousness. Simultaneous EEG could be proposed routinely in tilt test execution and become a determining factor in the choice of a therapeutic option.

Neurophysiological evaluation of areflexia in Holmes-Adie syndrome.

PURPOSE: To evaluate ankle areflexia in Holmes-Adie syndrome (HAS). PATIENTS AND METHODS: Hoffmann (H) and Tendon (T) soleus reflexes, tonic vibration reflex (TVR), and polysynaptic extension reflex of soleus muscle (PERS) were evaluated in eight patients with idiopathic HAS. Motor (MNCV) and sensory (SNCV) nerve conduction velocities, compound motor-action potential (CMAP), and sensory action potential (SAP) were also determined in upper and lower limbs. RESULTS: Soleus T reflex was obtained in one out of eight patients, and H-reflex was found in none of the patients. TVR was recorded in four out of eight patients, and PERS in all of the patients. MNCV, SNCV, CMAP and SAP showed normal values in all patients. In six out of the eight patients a late response following the tibial nerve stimulation showed constant latency, amplitude and morphology, with no recovery cycle or vibration inhibition. CONCLUSION: In this study, the neurophysiological spinal reflex circuitry evaluations support the view that HAS ankles areflexia is due to a selective impairement of monosynaptic connections of Ia afferents. A normal nuclear excitability is suggested by polysynaptic activation of the soleus motor nucleus.

Chronic inflammatory demyelinating polyneuropathy in diabetics: motor conductions are important in the differential diagnosis with diabetic polyneuropathy.

OBJECTIVE: It is important to recognize CIDP occurring in diabetics because, unlike diabetic polyneuropathy, it is treatable. The aim of this study was to find out whether there are clues which help to differentiate CIDP in diabetics from diabetic polyneuropathy. METHODS: We compared the electrophysiological and pathological findings of 7 diabetics, who developed a predominantly motor polyneuropathy with the features of CIDP, with a group of diabetics referred for symptomatic polyneuropathy. RESULTS: Of the 7 diabetics we believe developed CIDP, 6 met at least 3 and one patient two of the 4 electrophysiological criteria of demyelination. Of the 100 patients referred for diabetic polyneuropathy, only 4 fulfilled two criteria and none 3. Nerve biopsy findings were not helpful in differential diagnosis, as segmental demyelination and remyelination, onion bulbs and inflammatory infiltrates, which are the histologic features of CIDP, were also present in diabetic polyneuropathy. CONCLUSIONS: CIDP can be diagnosed in a diabetic patient when motor symptoms are predominant, are more severe than expected in diabetic polyneuropathy and 3 of the 4 electrophysiological criteria for demyelination are fulfilled. When only two criteria are met, we believe that a trial with one of the established treatments for CIDP may be helpful in confirming the diagnosis.

Approach to head trauma in childhood in a district general hospital.

The authors compared the management of children with head trauma in a general hospital in two different periods (1984-85 and 1988-90). In the first period 233 cases were retrospectively evaluated; no guidelines were available at that time. In the second period 709 paediatric patients were treated following a protocol with indications for hospital admission and diagnostic procedures. In the clinical classes of milder symptoms (S0, S1, S2) a statistically significant reduction of hospital admission (p < 0.05) and skull radiography (p < 0.001) was achieved with the protocol without increasing the number of diagnostic errors, the incidence of clinical worsening because of an intracranial lesion was the same in the two periods (1.28% vs 1.27%). From our data and from the literature it emerges that it is necessary to clearly distinguish the children from 10 to 14 years of age from the rest of the paediatric population for major risk of intracranial complications, as in this group the presence of a skull fracture represents a high risk factor, predictive of an intracranial haematoma. In the children under 10 years, the history and the clinical status have greater importance in establishing the diagnostic procedure to be followed. The asymptomatic cases (S0) or those with mild symptoms (S1) can be sent home with an instruction sheet explaining the symptoms of possible complications, without any further diagnostic procedures.

Ganglionic cyst of the deep peroneal nerve: description of a case.

The case of a patient with a small intraneural ganglion of the deep peroneal nerve is described, including the clinical and electrophysiological characteristics and the course four years after surgery.

Diagnosis and management of minor head injury: a regional multicenter approach in Italy.

Two series of patients admitted to the hospital after a minor head injury were collected in two different periods (1985 and 1989) in a regional hospital with a 24-hour computed tomography (CT) service, but without a neurosurgical unit. In 1988, a regional protocol on the management of patients with minor head injury (based on the presence of skull fractures in adults and on clinical parameters in children) was adopted. There was a 21% reduction in hospital admission in adults, and the number of skull x-ray films performed in children decreased significantly (p < 0.01). A more liberal use of CT examinations in asymptomatic patients with skull fractures produced an earlier identification of patients with extradural hematomas who were sent to neurosurgery before clinical deterioration with good results. Detection of cerebral contusions was clinically less important. Based on the availability of CT scanners in our area and on the results of our study, we have proposed new guidelines in management of minor head injury. The CT scans are obtained in patients with a Glasgow Coma Scale score of 13 or less. Skull x-ray films are obtained in patients older than 10 years with a Glasgow Coma Scale score of 14/15. If a fracture is found, the patient is sent to the nearest regional center for CT examinations. Children younger than 10 years are sent to a regional hospital with 24-hour CT availability for clinical observation or other indicated studies.

Orthostatic tremor: essential and symptomatic cases.

We studied clinically and electrophysiologically 8 patients affected by orthostatic tremor (OT), which is an unusual movement disorder consisting of shaking movements of the legs and trunk in the standing position. We failed to find any cause in 6 of the 8 cases. In 2 patients OT was clearly secondary to neurologic disease: hydrocephalus due to non-tumoral aqueduct stenosis and chronic relapsing polyradiculoneuropathy. The findings obtained suggest a relationship between OT and essential tremor (ET).

Epileptic transient amnesia.

A patient with epileptic amnesic attacks suffered three prolonged episodes similar to transient global amnesia. Clinical, electroencephalographic and neuropsychological observations during 2 years' follow-up are reported.

Lacunar infarcts: a personal series of 92 consecutive cases.

A series of 92 patients with lacunar infarcts identified by CT brain scan are described. Risk factors for cerebrovascular disease, clinical aspects and outcome are analyzed. Our cases show unusual clinical syndromes in a remarkable number of subjects, indicating the usefulness of performing a CT brain scan.

Skull fracture as a factor of increased risk in minor head injuries. Indication for a broader use of cerebral computed tomography scanning.

Two series of patients with a minor head injury (for a total of 182 cases), differing only in the presence and absence of a linear skull fracture, were admitted to a nonspecialized hospital and prospectively examined by computed tomography scanning. The presence of a fracture line proved to be significant, inasmuch as it was accompanied by approximately 38% of intracranial abnormalities versus 6% in the nonfracture cases. Early detection of any intracranial pathology that was still asymptomatic allowed prompt transfer of patients to the neurosurgical center, where operative treatment was carried out, when indicated, without mortality or morbidity. All operations (11 cases) were performed on patients with a fracture (105 cases) whereas none of the nonfracture patients (77 cases) required surgery. It is proposed that adult patients with minor head injuries with a skull fracture be submitted to computed tomography scanning in order that intracranial lesions may be detected, and treated, before the onset of clinical deterioration.

A prospective clinical and epidemiological study of head injuries in northern Italy: the Comune of Ravenna.

An analysis of all the head injuries occurring during one year within a well-defined geographical area was conducted in the region served by the Ravenna City Hospital in Northern Italy. This hospital does not have a neurosurgical service, so that patients suspected of having neurosurgical problems are transferred to the neurosurgical unit in Bologna, a distance of 65 Km (40 mi.). Of the 1468 head-injured patients seen in the emergency room, 644 (44%) were hospitalized, with an incidence of 372/10(5) pop/year) and were subjected to X-ray study of the skull (83%), EEG (64%), and CT scan (7.5%). 9 patients were transferred to the neurosurgical unit as emergencies on a clinical basis only, all were found to harbor cerebral lesions, and 7 were operated on. Of the patients hospitalized and subjected to CT scan in Ravenna, only one (0.17%) was found to have a lesion necessitating surgery. Mortality was 7.2% with 83% of these patients dying before admission. Three-month follow-up examination revealed the persistence of some symptoms in 20% of the 379 patients examined, but 91% had already returned to their previous occupation. Analysis of the risk factors present in the patients admitted to a non-specialized hospital seems to show that the presence of skull fracture, abnormal EEG, and alteration of the clinical condition constitute the indications for a CT scan, in order to detect the presence of intracranial lesions.(ABSTRACT TRUNCATED AT 250 WORDS)

Isolated sixth nerve palsy due to intracavernous carotid aneurysm in a young woman.

A large intracavernous carotid aneurysm was angiographically demonstrated in a 29 years old woman suffering from a persistent isolated abducens nerve palsy. CT brain scan failed to reveal the lesion. The usefulness of performing angiography in the cases of isolated abducens palsy of undetermined nature, is stressed.