Treatment of acute cluster headache with 20 mg sumatriptan nasal spray – an open pilot study

We investigated the efficacy and tolerability of 20 mg sumatriptan nasal spray in the acute treatment of cluster headache attacks in an open-label study. 10 patients met the criteria of the International Headache Society (IHS) for episodic or chronic cluster headache and were enrolled in our study. The primary efficacy measure was “pain free” 30 minutes after treatment. Secondary endpoints included “headache response” (defined as headache improvement from “very severe”, “severe” or “moderate” pain to “mild” or “no” pain) 15, 30, 45 and 60 minutes after treatment. We also assessed the participant's overall treatment satisfaction at the end of the study. Sumatriptan nasal spray was applied in 154 “moderate” to “very severe” cluster headache attacks. 30 minutes after nasal spray application, 50 % of attacks were completely aborted and 58 % of attacks responded to treatment. The overall efficacy of sumatriptan nasal spray was considered “excellent” in two, “good” in four, “reasonable” in two and “poor” in two patients. Eight patients indicated their intention to treat further attacks with intranasal sumatriptan. Seven patients were interviewed after a follow-up period of six months. Four patients continued to treat all cluster headache attacks with the intranasal sumatriptan formula, two patients had switched to subcutaneous sumatriptan and one patient was in remission since the end of the study. We conclude that 20 mg sumatriptan nasal spray might be an alternative therapy for the treatment of cluster headache attacks, but double-blind studies are needed to further evaluate its efficacy. Received: 26 March 2001, Received in revised form: 13 June 2001, Accepted: 18 June 2001     

Causes and place of death in Italian patients with amyotrophic lateral sclerosis

Spataro R, Lo Re M, Piccoli T, Piccoli F, La BellaV. Causes and place of death in Italian patients with amyotrophic lateral sclerosis.
Acta Neurol Scand: 122: 217–223.
© 2010 The Authors Journal compilation © 2010 Blackwell Munksgaard. Objectives – To determine the causes and place of death in a cohort of Italian patients with amyotrophic lateral sclerosis (ALS). A better understanding of the likely causes of death in ALS might improve the palliative care at the end‐of‐life, whereas knowing the place of death will help to verify the need for highly specialized care services, e.g. hospice and nursing home. Patients and methods – Between 2000 and 2008, 182 ALS patients (onset: spinal, 127; bulbar, 55; M/F: 1.6) were followed in a single ALS Tertiary Centre in Palermo, Sicily, Italy until death. Medical data for each individual patient were recorded in a large database throughout the disease course. Information concerning causes and place of death were obtained by consultation with relatives or the family physician. Results – Respiratory failure (terminal respiratory insufficiency, pneumonia) was the most frequent cause of death (81.3%), which included six cases (3.3%) who requested a terminal sedation. Sudden death and death during sleep accounted for by 6.0% and 6.6% of all deaths, respectively. Heart‐related causes of death were relatively infrequent in our cohort, accounting for by 7.1% of all deaths (i.e. sudden death: 6.0% and myocardial infarct: 1.1%). Patients (85.2%) died at home. Conclusions – The leading cause of death in ALS remains the respiratory failure, followed by the sudden death and death during sleep. Most patients in our cohort died at home, a choice that might be only partially driven by cultural factors. These findings might have a great impact on the development of the advanced and end‐of‐life palliative care and in the planning of specialized care services, as hospice and nursing home.     

The influence of baseline prognostic variables on outcome after thrombolysis

Thrombolysis increases case fatality but reduces the proportion of disabled survivors in recent trials in acute ischaemic stroke, although some trials show much higher mortality rates than others. One possible explanation for the different outcomes between trials is that the treatment effect with thrombolysis varies with baseline prognostic factors such as stroke severity. We examined the interaction between baseline risk and thrombolysis on outcome using individual patient data from the Multicentre Acute Stroke Trial–Italy (MAST-I). A multiple logistic regression of the MAST-I data was performed to identify which factors, identifiable at randomisation, most strongly predict a poor functional outcome. We then stratified the patients into those with severe strokes and those with mild strokes and examined the effect of thrombolysis on (a) case fatality and (b) dependency at 6 months after the stroke in the 157 patients who received streptokinase alone and the 156 controls. Streptokinase was found to cause an absolute increase of about 3% in case fatality in both “severe” and “mild” strokes; however, there was a 12% reduction in the number of dead or dependent “mild” strokes but a 6% increase in “severe” strokes. The number of patients was small, and therefore neither finding was statistically significant. In this exploratory analysis, the hazard with streptokinase appears similar in “severe” and “mild” strokes, but the benefit may be greater in “mild” strokes. Thrombolysis may be more effective in patients with “mild” strokes, but more information is required to confirm this hypothesis. Received: 29 January 1999 Received in revised form: 13 April 1999 Accepted: 5 May 1999     

The opinion of caregivers on aspects of schizophrenia and major affective disorders in a Nigerian setting

Background In Nigeria the burden of caring for persons with severe mental disorders rests largely on families whose attitudes to these conditions have not been explored. Objectives To assess the opinion of relatives of 75 schizophrenics and 20 major affective disorder cases on aspects of the disease and compare with the responses of relatives of cancer, infertility and sickle cell disease (SCD) cases. Method Caregivers were assessed using a burden questionnaire that contained items on etiological beliefs and attitudes to illness. Results The responses of relatives of the two psychiatric illness groups were similar. The single most important etiological factors were that “it is Satan's work” (35.8 %) and “it is a natural illness“ (23.2 %). Other factors were “genetic” (9.5 %), “witchcraft” (10.5 %) and “curse by enemies” (10.5 %). This was similar to the opinion of cancer and infertility caregivers; but different from SCD where the most important causative factors were “genetic” (41.5 %) and “natural” (21.5 %). Psychiatric caregivers had higher frequency of anger and stigma. Over two-thirds of psychiatric caregivers felt glad caring for the patient and would not like the patient institutionalized. Most families were thought to be supportive and there was an impression that caring had made family emotional ties closer. Conclusions These families were tolerant and would cooperate with health authorities. Causative models are influenced by available knowledge and practices in the culture. To actualize the potential of families to play useful community psychosocial roles, there is a need for public mental health literacy and welfare support. Accepted: 10 July 2001     

Homozygous exon 7 deletion of the SMN centromeric gene (SMN2): A potential susceptibility factor for adult-onset lower motor neuron disease

Mutations in the telomeric copy of the SMN gene (SMN1) are responsible for almost all infantile motor neuron disease (MND). In contrast, the role of the centromeric copy of the SMN gene (SMN2) in MND remains unclear. We searched for deletions of SMN1 and SMN2 in a group of 11 patients with sporadic adult-onset lower motor neuron disease (also referred to as “progressive muscular atrophy”) and found an excess of patients carrying homozygous deletions of SMN2 exon 7 (36 % versus 5 % in the normal population). This result suggests that SMN2 deletions could act as a susceptibility factor for sporadic lower motor neuron disease in adults. Received: 8 April 2001, Received in revised form: 22 June 2001, Accepted: 28 June 2001     

Influence of cerebral lesion volume and lesion distribution on event-related brain potentials in multiple sclerosis

Neurocognitive involvement in multiple sclerosis (MS) is heterogeneous with some authors suggesting a frontal pattern in patients with predominantly frontal lesions. To assess the relationship between the distribution of lesions and two cognitive components (visual N2, auditory P3a) of the event-related brain potential (ERP) receiving contributions from frontal lobe structures, we performed a combined ERP and magnetic resonance imaging (MRI) study. Thirty-four MS patients were assigned to “low lesion volume, (LLV)”(n = 12), “high lesion volume, (HLV)” (n = 12) and “frontal lesion volume, (FLV)” (n = 10) groups according to lesion volume and distribution on T2-weighted MRI-scans of the brain. ERPs in visual and auditory classification tasks as well as neuropsychological tests were carried out in patients and control subjects (n = 15). The index for automatic feature registration, the N2 component with its mainly frontal contribution in the visual task, was significantly reduced in amplitude in the FLV and HLV groups (both p < 0.01 vs. controls). Moreover its amplitude correlated with lesion volume (r=0.64, p < 0.001). In contrast neither P3a nor P3b subcomponents with a multiple generator nature in the auditory task varied systematically with lesion volume or distribution. Total lesion volume rather than predominant lesion arrangement appears to be the most important factor in neurocognitive changes in MS. This is most consistent with the view that MS lesions lead to partial disconnections within widespread cortical networks which in turn produce a pattern of neuropsychological deficits that reflect total lesion load more than lesion distribution. Received: 23 August 2000, Received in revised form: 11 January 2001, Accepted: 10 April 2001     

Retrospective study of a large population of patients affected with mitochondrial disorders: clinical, morphological and molecular genetic evaluation

Mitochondrial disorders are human genetic diseases with extremely variable clinical and genetic features. To better define them, we made a genotype-phenotype correlation in a series of 207 affected patients, and we examined most of them with six laboratory examinations (serum CK and basal lactate levels, EMG, cardiac and EEG studies, neuroradiology). We found that, depending on the genetic abnormality, hyperckemia occurs most often with either chronic progressive external ophthalmoplegia (CPEO) and ptosis or with limb weakness. Myopathic EMGs are more common than limb weakness, except in patients with A8344G mutations. Peripheral neuropathy, when present, is always axonal. About 80 % of patients with A3243G and A8344G mutations have high basal lactate levels, whereas pure CPEO is never associated with increased lactate levels. Cardiac abnormalities mostly consist of conduction defectsAbnormalities on CT or MRI of the brain are relatively common in A3243G mutations independently of the clinical phenotype. Patients with multiple mtDNA deletions are somehow “protected” against the development of abnormalities with any of the tests. We conclude that, despite the phenotypic heterogeneity of mitochondrial disorders, correlation of clinical features and laboratory findings may give the clinician important clues to the genetic defect, allowing earlier diagnosis and counselling. Received: 8 December 2000 / Received in revised form: 18 February 2001 / Accepted: 13 March 2001     

Longitudinal MRI study of multiple system atrophy – when do the findings appear,and what is the course?

Several investigators have revealed features of multiple system atrophy (MSA) by magnetic resonance imaging (MRI). For use in clinical diagnosis, we determined the exact time when two main features of pontine and putaminal intensity changes appeared. Furthermore, in order to reveal the course from when the disorder first appeared and how it spread, we also investigated the course of MRI findings and differences between clinical subtypes. The cranial MRI of 42 patients with MSA were longitudinally studied including comments on the so called “cross sign” of pontine T2 high intensity, which was divided into 6 stages, and also on the linear T2 high intensity of the dorsolateral side of the putamen (“putaminal slit”) which was divided into 4 stages. Patients were classified as 16 MSA-C, 7 autonomic dominant type (MSA-A), and 19 MSA-P. The age at onset ranged from 41 to 74 years (mean, 55 ± 9). The duration of the disease in the MRI study ranged from 1 to 24 years. The pontine “cross sign” was completed (shows Cross, stage IV) earlier in MSA-C mainly before 5 years, later in MSA-P and even much later in MSA-A. Regarding the “putaminal slit”, MSA-P shows earlier bilateral changes (stage II), mostly before 3 years, compared with MSA-C, which requires 4 years to reveal even a unilateral change (stage I), or MSA-A which requires even more time. MRI findings showed a tendency to relate to clinical findings, since MSA-C exhibits “cross sign” completion earlier than bilateral “putaminal slit”; however, MSA-P shows bilateral “putaminal slit” earlier than “cross sign”, and MSA-A requires much more time to show both. Clinically, MSA-C, MSA-A, or MSA-P showed different MRI courses so that three subtypes could be defined also with MRI findings. Therefore these observations are useful not only for diagnosis of MSA itself, but also to distinguish clinical subtypes (MSA-C, MSA-A, or MSA-P) which have different rates of lesion progression. Received: 5 September 2001, Received in revised form: 10 December 2001, Accepted: 17 December 2001     

Discontinuation of mechanical ventilation in patients with amyotrophic lateral sclerosis

Mechanical ventilation, both invasive and non-invasive, may be an effective means of improving the quality of life and prolonging the survival of patients suffering from amyotrophic lateral sclerosis (ALS). However, the attitude towards this palliative measure varies greatly between different centres and countries. One of the arguments cited against this procedure is the fear that a patient might request the physician to discontinue life support. We believe that the question of withdrawal of mechanical ventilation can only be meaningfully addressed in the general context of palliative care. Here, we review possible modes of action in response to a patient’s request for life support withdrawal and their medical, legal and ethical implications. We propose that the following goals should be pursued: (1) prevention of unwanted ventilation by early, open discussion with patient and relatives, (2) delivery of optimal palliative care by the caring team, (3) recognition of the patient’s right to withdraw his/her consent to an invasive medical procedure. If these goals have been met, it may be medically, legally and ethically justified for the physician to take all necessary steps to ensure a peaceful death after discontinuation of life support. Received: 24 November 1997 Received in revised form: 3 April 1998 Accepted: 5 April 1998     

The two faces of Alzheimer's disease

Correct classification of patients with dementia is pertinent to proper interpretation of research findings. However, the history of Alzheimer's disease (AD) is characterized by a continuing debate on its nosological status. Cerebrovascular pathology, Lewy bodies, or hippocampal sclerosis in combination with neuropathological signs of AD of only limited severity results in a disease that is essentially different from severe, purely degenerative AD. The clinical signs, course of the disease, and pathological correlates in elderly patients suffering from “mixed dementia of the Alzheimer type,” may differ from those with “purely degenerative Alzheimer's disease” as encountered in relatively young patients. Both clinicians and researchers have much to gain from a perspective that acknowledges the differences between these subgroups of AD patients. It may provide a more realistic perspective, and it holds promise for new opportunities for prevention and treatment. Received: 16 October 1999, Received in revised form: 13 December 1999, Accepted: 12 January 2000     

A critique of ancillary tests for brain death

The acceptance of brain death by society has allowed for the discontinuation of “life support” and the transplantation of organs. The standard clinical criteria for brain death, when rigorously applied, ensure that the brainstem is destroyed. Because more rostral structures are more vulnerable than the brainstem, these are almost invariably devastated when brainstem function is irreversibly lost as a result of whole brain insults. Then, clinical criteria for “brainstem death” ensure that “whole-brain death” is present. However, if the brainstem is selectively damaged or if brainstem function cannot be adequately assessed clinically, ancillary tests are needed to confirm whole-brain death with certainty. Ancillary tests are also required in very young children. In addition, some societies require their use as a matter of principle. Only tests of whole-brain perfusion adequately serve these purposes.     

How many camels are there in Italy? Cognitive estimates standardised on the Italian population

Objective: We provided the standardisation of a new Cognitive Estimation Task (CET). Participants: the test was administered to 175 healthy subjects. Results: performance on the Cognitive Estimation Task (CET) is associated with gender (where women show poorer performance than men) and education (where more highly educated individuals show better performance compared to individuals with lower levels of education). However ,CET performance is not associated with age. Discussion: the lack of age effects on the CET may be explained by the task dependence on “crystallised intelligence”, which is less affected by healthy adult ageing than “fluid intelligence”. Received: 2 September 2002 / Accepted in revised form: 28 January 2003 This paper was presented in preliminary form at the annual meeting of Italian Neurological Society (SIN), Rimini, 2001. Correspondence to: L. Sacco     

The insomnia plague: a Gabriel García Márquez story

“All the great writers have good eyes” is a sentence by V. Nabokov that is very suitable for G.G. Márquez and his One Hundred Years of Solitude. The novel, published in 1967, introduces among many others, the character of little Rebeca, whose frailness and greenish skin revealed hunger “that was older than she was”. The girl, because of a pica syndrome, only liked to eat earth and the cake of white-wash. But her fate appears to be determined by the lethal insomnia plague, whose most fearsome part was not the impossibility of sleeping but its inexorable evolution toward a loss of memory in which the sick person “sinks into a kind of idiocy that had no past”. Rebeca's lethal insomnia looks quite similar to the “peculiar, fatal disorder of sleep” originally described by Lugaresi et al. in 1986. One Hundred Years of Solitude shows that G.G. Márquez was gifted not only with good eyes, but has the seductive power of changing reality into fantasy, while transforming his visions into reality. Received: 9 June 2000 / Accepted in revised form: 2 October 2000     

Lumbar puncture and the risk of herniation: when should we first perform CT?

Death following lumbar puncture (LP) is feared by physicians. Many opinions are found in literature on the question whether computed cranial tomography (CT) should be performed before LP, to prevent herniation. These opinions are mainly based on retrospective studies and pathophysiological reasoning. In this review the difficulties in the decision whether we should perform CT before LP are discussed. It is explained that the concept of “raised intracranial pressure” is confusing, and that the less ambiguous terms “brain shift” and “raised CSF pressure” should be used instead. Brain shift is a contraindication to LP, whether CSF pressure is raised or not, and whether papilloedema is present or not. Subsequently, recommendations are offered for indications to perform CT before LP, grouped according to the safety and clinical utility of LP. Received: 28 May 2001, Accepted: 24 July 2001     

Limitations in randomised controlled trials evaluating drug effects in mania

Functional neuroimaging findings of “hypofrontality” in schizophrenic patients – as tested with the Wisconsin Card Sorting Test (WCST) – are still controversial, mainly due to methodological aspects and the heterogeneity of the patient samples. To measure WCST specific and reproducible reduced cerebral activations in schizophrenic patients, we revised the study design and patient recruitment, respectively. For this purpose, we used an adequate active control task instead of an undefined rest condition to determine exclusively WCST specific cerebral activations. In addition, we focused on the investigation of modified activations between a selected group of neuroleptic-naive schizophrenic patients and carefully matched healthy controls by means of functional magnetic resonance imaging. The results indicate that neuroleptic-naive schizophrenic patients show reduced activations in the right frontal and left temporal lobe, as well as in the left cerebellum. By utilizing an active control task all unwanted activations are suppressed. Furthermore the influence of different task performances is reduced. The findings are in line with previous PET and SPECT studies and confirm the “hypofrontality” hypothesis. The findings suggest that “hypofrontality” is not caused by neuroleptic medication. Received: 11 October 2000 / Accepted: 13 February 2001     

Obsessional personality features in employed Japanese adults with a lifetime history of depression: assessment by the Munich Personality Test (MPT)

Background Although a number of studies have reported on the association between obsessional personality features as measured by the Munich Personality Test (MPT) “Rigidity” scale and depression, there has been no examination of these relationships in a non-clinical sample. Methods The dimensional scores on the MPT were compared between subjects with and without lifetime depression, using a sample of employed Japanese adults. The odds ratio for suffering from lifetime depression was estimated by multiple logistic regression analysis. To diagnose a lifetime history of depression, the Inventory to Diagnose Depression, Lifetime version (IDDL) was used. Results The subjects with lifetime depression scored significantly higher on the “Rigidity” scale than the subjects without lifetime depression. In our logistic regression analysis, three risk factors were identified as each independently increasing a person's risk for suffering from lifetime depression: higher levels of “Rigidity”, being of the female gender, and suffering from current depressive symptoms. Conclusion The MPT “Rigidity” scale is a sensitive measure of personality features that occur with depression. Received: 3 January 2001 / Accepted: 10 April 2001     

Similar topographical distribution of neurofibrillary tangles in amyotrophic lateral sclerosis and parkinsonism–dementia complex in people living in the Kii peninsula of Japan suggests a single tauopathy

The presence of many neurofibrillary tangles (NFTs) in the central nervous system is a hallmark of amyotrophic lateral sclerosis (ALS) and parkinsonism–dementia complex (PDC) in people living in the Kii peninsula of Japan and in the island of Guam. To determine whether or not ALS and PDC are on a spectrum of a single tauopathy, we investigated the topography of NFTs semiquantitatively in two patients with ALS, three with PDC, and two with “PDC plus ALS” (PDC followed by ALS) on the basis of clinical symptoms. NFTs were counted under ×100 magnification of Gallyas-Braak stained preparations and were plotted on brain maps of the hemisphere, brainstem, and the spinal cord. In all cases, the hippocampus, particularly in the CA1 field, the parahippocampal gyrus, amygdaloid nucleus, and the temporal poles were most severely affected. In the neocortex, layers II–III were more severely affected by NFTs than layers V–VI. In the spinal cord, a few NFTs were revealed in the intermediate gray. NFTs were dense in all cases of PDC and “PDC plus ALS” and variable in density in ALS cases, although the topography was similar between them. We conclude that similar topographical distribution of NFTs in ALS and PDC in people living in the Kii peninsula of Japan suggests a single tauopathy.     

The diagnostic accuracy of magnetic resonance imaging and cerebrospinal fluid cytology in leptomeningeal metastasis

Diagnostic decision making in the case of patients suspected of having leptomeningeal metastasis (LM) can be very difficult. The results of cerebrospinal fluid (CSF) cytology can be repeatedly negative, and the predictive value of gadolinium-enhanced magnetic resonance imaging (MRI) is not well known. We report the results of CSF cytology and Gd MRI in 61 patients with known cancer, suspected of having LM. We combined our data with those from a similar study and calculated the sensitivity and specificity of CSF and Gd MRI, in the absence of a “gold standard diagnosis.” CSF cytology was positive for LM in 35 patients and MRI in 38. With CSF cytology sensitivity 75% and specificity 100%, with Gd MRI sensitivity was 76% but specificity only 77%. We conclude that Gd MRI provides strong support in the diagnosis of LM in patients with cancer who have negative results on CSF cytology. Received: 6 July 1998 Received in revised form: 15 January 1999 Accepted: 3 March 1999     

Retrospective study of a large population of patients with asymptomatic or minimally symptomatic raised serum creatine kinase levels

A retrospective evaluation of asymptomatic subjects with persistent elevation of serum creatine kinase (CK) levels (hyperCKemia) was made in order to verify the presence of subclinical myopathy or idiopathic hyperCKemia and to define the most appropriate diagnostic pathway. Persistently increased serum CK levels are occasionally encountered in healthy individuals. In 1980 Rowland coined for them the term idiopathic hyperCKemia. Despite the increase of scientific knowledge, several healthy subjects with hyperCKemia still represent a problem for the clinician. We made a retrospective evaluation of 114 asymptomatic or minimally symptomatic individuals with incidentally detected persistent hyperCKemia. They underwent neurological examination and laboratory/instrumental evaluation. Skeletal muscle biopsy was performed and thoroughly investigated. Biochemical and genetic investigations were added in selected cases. Logistic regression analysis was applied. We diagnosed a neuromuscular disorder in 21 patients (18.4 %), and found, by muscle biopsy and/or EMG, pathological but not conclusive findings in 57 subjects (50 %). The statistic correlation between elevated serum CK levels and the probability of making a diagnosis changed according to the age of the patient. Conclusions Muscle biopsy is the basic tool for screening asymptomatic subjects with hyperCkemia. It allowed us to make a diagnosis of disease in 18.4 % of patients, and to detect skeletal muscle abnormalities in 38.6 % of the subjects. Interestingly, 31.6 % of individuals had completely normal muscle findings. These best fit the “diagnosis” of idiopathic hyperCKemia. Received: 13 March 2001, Received in revised form: 3 July 2001, Accepted: 5 July 2001     

Death, euthanasia and end-of-life decisions according to the relatives' perspective -- a survey after the death of a close relative

Empirical research on euthanasia and medical decisions at the end of life usually focus on the doctors' perspective. The perspectives of patients, relatives respectively the bereaved families have been neglected so far. The project "Patients as partners. Tumour patients and their participation" aims to improve the participation of tumour patients in medical decision making at the end of life by means of several offerings for patients. In order to develop a theoretical model, interviews were conducted with patients, relatives, doctors and members of the bereaved families. Between March 2002 and July 2004 questionnaires were sent to the bereaved families about eight to ten weeks after their relatives had perished. Before dying, the patients had been looked after and offered consultation by a palliative care team either in hospital or at home. RESULTS: Of 151 sent out questionnaires, 59.6 % (n = 90) were filled in and sent back by members of the bereaved families. 52.3 % of the patients had died in hospital, 33.7 % in their private home. All of the patients who died at home, but only one in three patients who died in hospital also wanted to die there. The relatives were predominantly very satisfied or satisfied with the medical care (67.8 %). 11 % of the bereaved families said, their dying relatives had seriously asked for euthanasia. In 74.4 % of all cases, decisions for the renunciation of therapy were made, mostly due to a worsening of the general condition (54.4 %) or a progress of the disease (46.6 %). CONCLUSION: The questioning was successfully conducted. Members of bereaved families are able and also prepared to answer questions about the last days of their relatives lives. The question about the desired dying place has proved to be workable. In empirical research, the perspective of the relatives and bereaved families should be taken in to account seriously.