Mapping of a gene for Parkinson's disease to chromosome 4q21-q23.

Parkinson's disease (PD) is the second most common neurodegenerative disorder after Alzheimer's disease, affecting approximately 1 percent of the population over age 50. Recent studies have confirmed significant familial aggregation of PD and a large number of large multicase families have been documented. Genetic markers on chromosome 4q21-q23 were found to be linked to the PD phenotype in a large kindred with autosomal dominant PD, with a Zmax = 6.00 for marker D4S2380. This finding will facilitate identification of the gene and research on the pathogenesis of PD.

Peripheral nervous system involvement in Klippel-Trenaunay syndrome.

Klippel-Trenaunay syndrome (KTS) is a rare congenital malformation of unknown etiology characterized by cutaneous hemangiomas, venous varicosities and bony and soft tissues hypertrophy usually affecting one limb. Several complex anomalies involving various organs and systems have been described, whereas involvement of the peripheral nervous system has rarely been reported in KTS. We describe the case of a 67-year-old woman with KTS and peripheral neuropathy related to the presence of epineurial microscopic arteriovenous anastomoses (AVA) and endoneurial vascular coils in sural nerve biopsy from both hypertrophic and non-hypertrophic limb. The maintenance of AVA has been proposed to be the cause of the hypertrophy. The observation in our patient of AVA in non-hypertrophic limb contrasts with this hypothesis.

Lack of sodium channel mutation in an Italian family with paramyotonia congenita.

OBJECTIVE: To conduct the genotype-phenotype correlation in a family in which several individuals share clinical and electrophysiologic features of paramyotonia congenita (PC). BACKGROUND: PC, hyperkalemic periodic paralysis (HyperPP), and potassium-aggravated myotonias form the group of hereditary sodium channelopathies. Each of these disorders is associated with different point mutations in SCN4A, the gene encoding the alpha-subunit of the adult human skeletal muscle sodium channel. However, in HyperPP families, evidence of a causative gene different from SCN4A has been found. METHODS: We conducted direct clinical examination, electrophysiologic (EMG/electroneurographic) and cardiologic studies, as well as laboratory screening in several affected and nonaffected members of the family. We performed the genotype-phenotype correlation by microsatellite linkage and cDNA-mutation analyses of the SCN4A gene. RESULTS: Affected members in this family showed clinical and electrophysiologic features typical of PC. The disease phenotype segregated with the chromosomal region that includes the SCN4A gene. Analysis of the entire cDNA sequence of the SCN4A gene in the index case disclosed a G3826A transition, which results in the Val1276Ile substitution. However, PCR-single-stranded confirmation polymorphism and direct sequencing analysis of the segment coding for Val-1276 on genomic DNA confirmed the G3826A transition in the index case but was negative in 11 affected members of the family; however, neither mutations nor aberrant splicings causative of the PC phenotype in this family were found on SCN4A. CONCLUSION: The existence of a second gene different from SCN4A that can give rise to a clinical PC phenotype can be speculated upon.

Cognitive impairment in systemic lupus erythematosus: a follow-up study.

We evaluated outcome and the clinical value of cognitive impairment in systemic lupus erythematosus (SLE). Fifty-one consecutive SLE subjects with or without overt nervous system involvement received two comprehensive neuropsychiatric and neuropsychological assessments, including the Mental Deterioration Battery, the Mini Mental State Examination (MMSE), and tests from the Wechsler Adult Intelligence Scale. The two neuropsychological assessments were made when subjects were in stable neurological condition. Twenty-seven patients were found to have neuropsychiatric symptoms (NP-SLE) at the first assessment, and three others developed them during the follow-up. Fifteen patients (10 NP-SLE) had cognitive impairment at the first assessment. At retest the cognitive deficit persisted in all patients but one (non-NP-SLE) and had developed in four others. In the cognitively impaired subjects scores on MMSE approached the cutoff for an overt dementing condition. No progressively decreasing scores were found on any of the tests. No relationships were shown between neuropsychological diagnosis and neuropsychiatric disorder, neuroradiological findings, disease activity, or steroid and nonsteroid immunosuppressive therapy. Cognitive impairment thus seems to be a stable symptom of CNS involvement in SLE. It corresponds to the subjective complaint of intellectual difficulties and marginal performance on the MMSE. Intellectual deterioration may occur in patients without other symptoms of NP-SLE. Standardized neuropsychological testing methods should be used routinely to assess SLE patients.

[Peripheral nervous system involvement in HCV-related mixed cryoglobulinemia] / Interessamento del sistema nervoso periferico nella crioglobulinemia mista HCV-correlata.

In HCV-related mixed cryoglobulinemia (MC) a peripheral neuropathy (PN) may occur. To evaluate the prevalence and the characteristics of PN, 133 consecutive patients with HCV-MC (117 type II, 16 type III) were studied. Neurologic evaluation was performed according to the guidelines of Italian Group for the Study of Cryoglobulinemias, using a neurological disability score and a neurological symptom score. In 52/133 patients an electrophysiologic study (ENG) of ulnar, peroneal and sural nerves was performed. For 27/52 patients ENG data registered at different times (interval 12-96 months) were available. In 11 patients a sural nerve biopsy was obtained. An overt PN, mostly as sensory asymmetrical or symmetrical nerve impairment, was found in 107/133 patients (80.4%). ENG abnormalities-reduction or absence of sensory and sometimes of motor action potential, normal or slightly impaired nerve conduction velocity, consistent with axonal damage- were detected in 48/52 patients (92.3%). In 26 out of the 27 patients observed at different times an evolution of PN was found. Nerve biopsies showed a prevalent axonal damage, swollen endothelial cells in epi- and perineurial vessels and scarce mononuclear perivascular infiltrates. No leukocytoclastic vasculitis was observed. Immunoglobulins and complement in sub-perineurial vessel wall were detected. CONCLUSIONS: In HCV-MC a PN is frequent. It is mostly a sensory and progressively worsening axonopathy. Different mechanisms may be involved in the pathogenesis of this disorder and a direct role of HCV cannot be excluded.

[Anastomosis of the thoracic duct and the esophagus in surgical treatment of cholestasis. Experimental research]. / Anastomosi fra dotto toracico ed esofago nella terapie chirurgica della colestasi. Ricerche sperimentali.

After brief recall of the pathophysiology of cholestasis, the authors describe a technic of internal drainage of lymph from the thoracic duct by an indirect anastomosis created surgically between the latter and the esophaghus. They conclude that the procedure definitely solves certain symptomatologic aspects of cholestasis, but has no effects on the underlying anatomopathological lesion, which does not regress once established.

[Preliminary study of ultrastructural changes of the gastric mucosa due to cholecysto-gastrostomy. Experimental research]. / Studio preliminare delle alterazioni ultrastrutturali della mucosa gastrica in seguito a colecisto-gastrostomia. Ricerche sperimentali.

After reviewing the literature on anatomo-histological lesions of the gastric mucosa in so-called "biliary reflux gastritis", the Authors undertook an experimental study of ultrastructural alterations of the gastric mucosa after cholecysto-gastrostomy operation conducted in the dog. In this preliminary note they report the alterations observed 60 days after the operation and consider it necessary to continue observations for a longer space of time after the operation.

[Ileo-ileo-colic invagination due to pure fibroma of the small intestine. Personal observation (author's transl)]. / Invaginazione ileo-ileo-colica da fibroma puro del tenue. Osservazione personale.

Starting from a case of pure fibroma of the small intestine, which led to ileo-ileo-colic invagination, the Authors review the literature on the subject. The great rarity both of the type of neoplastic pathology found and the type of induced intestinal invagination is stressed. It is concluded by asserting that correct diagnosis, adequate selection of the type of surgery and its efficient performance allow a favourable prognosis in the overwhelming majority of cases.

[One stop surgery in pediatric surgery. Preliminary report]. / One-Stop Surgery in chirurgia pediatrica. Esperienza preliminare.

The One-Stop Surgery (OSS) is a new method of Day Surgery, which combines preoperative evaluation and subsequent operation into one visit. This report describes the initial experience of the authors. Referring physicians were informed by fax about method and selected surgical procedures. Included form helped them to gain anamnestic data and to inform parents about preoperative fast. Form was then sent back by fax to the pediatric surgeon and anesthesiologist who determined the patient suitability and scheduled the day of the surgery. At hospital admission, if the diagnosis was confirmed and no anesthesiologic contraindications were discovered, the patient underwent the prescheduled surgical procedure and was discharged as a day case. Another form containing informations about home postoperative care and telephone numbers for emergency call was gave to the parents. From November 2000 through February 2001 43 patients, aged from 2 to 7 years, underwent one-stop surgical procedure: central venous catheter removal (n = 16), umbilical (n = 2) and inguinal (n = 10) hernia repair, prepuce dorsal slit (n = 15). Recovery of all patient was uneventful. None of them called during the period considered necessary for postoperative follow-up. Decreased costs and increased satisfaction of the patients and parents are the most important advantages of the OSS. Potential disadvantages are a not appropriate indication for the planned procedure and/or an anesthesiologic contraindication at hospital admission. It could involve a waste of human and financial resources and an useless psychologic stress for the family. Authors conclude it is not advisable the OSS use on a large scale without a sound experience in pediatric Day Surgery.

[CHARGE association: report of a clinical case with anal atresia and rectovaginal fistula]. / Associazione CHARGE: descrizione di un caso clinico con atresia anale e fistola retto-vaginale.

CHARGE association is a non-random constellation of Coloboma, Heart Disease, Atresia of the choana, Retarded mental development and growth, Genital hypoplasia, Ear anomalies and deafness. We report on a newborn with CHARGE association. In addition to the typical features our case presented anal atresia and rectovaginal fistula. Our patient had congenital cardiopathy and feeding problems and died at the age of 3 months. Most case of CHARGE association appear to have a primary defect of pharyngeal incoordination that cause aspiration of secretion that is an important cause of death in the nonsurvivors.

[The VACTERL association: a report of a clinical case with hepatic cystic lymphangiectasis]. / Associazione VACTERL: descrizione di un caso clinico con linfangectasia cistica epatica.

VACTERL association includes three or more of the following six anomalies: V (vertebral anomalies), A (anal atresia), C (cardiac abnormalities), TE (tracheo-esophageal fistula and/or esophageal atresia), R (reno-urinary anomalies) and L (limb defects). VACTERL cases are classified as "associated" when other than the typical six defects are present in the same infant, or "isolated" when they are not. We report a case of VACTERL association "associated" that presents an hepatic cystic lymphangiectasia that was never described before in literature. We also consider the most important factors involved in the aetiology of the typical anomalies.

[Cerebral hemodynamics and major surgery]. / Emodinamica cerebrale e interventi chirurgici maggiori.

AIM: Near infrared spectroscopy (NIRS) is a non invasive optical technique to assess the monitoring of oxygenation and cerebral hemodynamics. Aim of our study was to value cerebral hemodynamics during major surgery to reduce the period of possible modifications of cerebral oxygenation. METHODS: Twenty-five newborns which underwent surgical intervention (8 diaphragmatic hernia, 8 esophageal atresia, 1 neck lymphangioma, 8 intestinal malformation) were studied during surgery by means of NIRS (NIRO 300), using an electrode applied to the scalp in the frontoparietal region. We monitored the Tissue Oxygenation Index (TOI) as well as the changes in concentration of total haemoglobin (tHb), oxygenated haemoglobin (O2Hb) and deoxygenated haemoglobin (HHb). The changes have been expressed as difference from the basal value recorded at the beginning of surgery. RESULTS: During the surgical intervention O2Hb, tHb and TOI decreased (DeltaO2Hb=-11.4+/-6.5 microM; P<0.001; DeltatHb=- 7.54+/-4.3 microM, P<0.05; microTOI=-12.5+/-5.5%, P<0.001), and HHb increased (DeltaHHb=+4.80+/-2.30 microM, P<0.001); the greatest changes occurred when the viscera were positioned into the abdomen (in diaphragmatic hernia and intestinal malformation). CONCLUSION: The present study suggests that NIRS, during major surgery, is able to monitor oxygenation and cerebral hemodynamics thus allowing a real time evaluation of some intraoperative procedure aftereffects that, if timely modified, could reduce cerebral hypoxia risks.

[Esophageal atresia and malformative association. Clinical contribution]. / Atresia esofagea e patologia malformativa associata. Contributo casistico.

AIM: Esophageal atresia (EA) is a congenital malformation with an incidence of 1/3,000-3,500 live birth, due to anomalies of the foregut. Although an interstitial deletion of chromosome 17 (q22q23.3) has been identified, the etiology seems to be multifactorial and not only genetic. The aim of this retrospective study is to evaluate the association of EA with chromosomal pathologies and/or malformation syndromes. METHODS: The authors report 18 cases of EA admitted to the UTIN of the Pediatric Department, University of Catania, between January 1998 and January 2001, and discuss the phases of preoperative stabilization, the operation, postoperative complications and the follow-up at 12 months. RESULTS: The results obtained concerning the association of EA with chromosomal diseases and malformation syndromes are described in the ''Results'' section of the paper. CONCLUSIONS: The results obtained, notwithstanding the low number of patients, show that the association of EA with chromosomal pathologies and malformation syndromes is relevant both from a numerical and prognostic point of view in comparison to the data published in the literature.

One-stop surgery in pediatric surgery. Aspects of anesthesia. Preliminary report.

AIM: One-Stop Surgery (OSS) is a new day surgery combining preoperative evaluation and subsequent operation in one medical examination. METHODS: This paper reports the authors' initial experience using this method. Referring physicians were informed of the methods and selected surgical and anesthetic procedures by fax. They were also faxed a form to fill in with case history details and instructions to the parents on the preoperative fast. The completed form was faxed back to the surgeon and pediatric anesthetist who determined patient suitability and scheduled hospitalization and surgery. On hospitalization physical examination was performed to confirm diagnosis and rule out contraindications for anesthesia. Patients considered suitable then underwent surgery and were discharged on the same day as a day case. The families were given instructions to be followed for home care and emergency telephone numbers. In the time interval November 2000 to February 2001 43 patients aged between 2 and 7 years were treated following this procedure for removal of a central venous catheter (16 patients), umbilical (2 patients) and inguinal (10 patients) hernia repair, and prepuce dorsal slit (15 patients). Anesthesia consisted of nasal premedication using midazolan, general inhalation anesthesia and peripheral locoregional block. RESULTS: The diagnosis of all chidren was confirmed. Only 1 patient with upper airway infection was discovered. Recovery of all patients was uneventful. None of the patients called during the postoperative follow-up period for adverse events. CONCLUSIONS: Low costs and major parent and patient satisfaction are the main advantages of OSS, while the possible disadvantages are inaccurate referral for surgery and detection of contraindications for anesthesia at admittance to hospital. The authors recommend the use of wide scale OSS only when the operators have sound experience in pediatric day surgery.

Familial amyloidotic polyneuropathy: description of an Italian kindred.

Familial amyloidotic polyneuropathy (FAP) is a heterogeneous group of genetic disorders characterized by progressive systemic deposition of extracellular amyloid fibrils, mainly affecting the peripheral nervous system (PNS). These disorders, inherited as an autosomal dominant trait, have frequently been described in various ethnic groups, but have rarely been reported in Italy. A 42 year-old man came to our observation for loss of pain and temperature sense in his legs. Clinical and laboratory data pointed to an amyloidotic polyneuropathy. This led us to discover a large italian kindred in which 19 members were affected by FAP. The diagnosis, established in 8 members on the clinical and laboratory findings, was ana-catamnestic in other 11. In this kindred the onset of the disease ranges from 35 to 50 years of age and the course is progressive and often fatal. The early symptoms are mainly related to autonomic disturbances and to peripheral neuropathy. Cardiac and renal involvement occurs frequently and may be life-threatening.

A new de novo mutation of the connexin-32 gene in a patient with X-linked Charcot-Marie-Tooth type 1 disease.

We report a 26-year-old Italian man with X-linked Charcot-Marie-Tooth (CMT) disease type 1 (CMT-X1) and a negative family history for neuromuscular diseases. Clinical and electrophysiological examinations of the patient's mother and siblings were normal. Molecular analysis by polymerase chain reaction--single-strand conformation polymorphism (PCR-SSCP) on genomic DNA from the patient and all members of his family revealed a C-to-T transition in codon 8 of exon 2 of the connexin-32 (Cx32) gene on the X chromosome only in the patient. This transition in the 5'-coding region, resulting in a Thr-Ile substitution, is likely to be the cause of CMT phenotype in our patient, and it represents a new de novo mutation of the Cx32 gene.

Clinical genetic analysis of Parkinson's disease in the Contursi kindred.

We performed a clinical genetic analysis of a kindred originating in the town of Contursi in Salerno province, Italy, in which 60 individuals in 5 generations are known to have had Parkinson's disease (PD). Two previously reported autopsy cases showed typical PD with Lewy bodies. The inheritance pattern is apparently autosomally dominant with a segregation ratio of 40.1% for kindred members aged 50 years and older. The mean age at PD onset is 45.6 years (standard deviation, 13.48; range, 20-85) with a mean course to death of 9.2 years (standard deviation, 4.87; range, 2-20). Otherwise, clinical characteristics of PD in the kindred, including variance in onset age and incidence of tremor and levodopa responsiveness, are similar to those of PD in the community. The presence of tremor tended to be concordant in affected parent-child pairs, but there was no parent-child correlation for age at onset or intrasibship clustering of tremor or onset age. A suggestion of anticipation disappeared after adjustment for age-related ascertainment bias. The findings show that a presumably single mutation can produce a heterogeneous PD phenotype, even among siblings. This is consistent with the hypothesis that PD in the community may in fact be caused by such a mutation, but one producing a lower penetrance and older age at onset than those in this kindred.