MRI Patterns in Pediatric CNS Hemophagocytic Lymphohistiocytosis.

BACKGROUND AND PURPOSE: Neuroimaging has an important role in detecting CNS involvement in children with systemic or CNS isolated hemophagocytic lymphohistiocytosis. We characterized a cohort of pediatric patients with CNS hemophagocytic lymphohistiocytosis focusing on neuroradiologic features and assessed whether distinct MR imaging patterns and genotype correlations can be recognized. MATERIALS AND METHODS: We retrospectively enrolled consecutive pediatric patients diagnosed with hemophagocytic lymphohistiocytosis with CNS involvement treated at 2 pediatric neurology centers between 2010 and 2018. Clinical and MR imaging data were analyzed. RESULTS: Fifty-seven children (40 primary, 70%) with a median age of 36 months (interquartile range, 5.5-80.8 months) were included. One hundred twenty-three MR imaging studies were assessed, and 2 broad imaging patterns were identified. Pattern 1 (significant parenchymal disease, 32/57, 56%) was seen in older children (P = .004) with worse clinical profiles. It had 3 onset subpatterns: multifocal white matter lesions (21/32, 66%), brainstem predominant disease (5, 15%), and cerebellitis (6, 19%). All patients with the brainstem pattern failed to meet the radiologic criteria for chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids. An attenuated imaging phenotype (pattern 2) was seen in 25 patients (44%, 30 studies) and was associated with younger age. CONCLUSIONS: Distinct MR imaging patterns correlating with clinical phenotypes and possible genetic underpinnings were recognized in this cohort of pediatric CNS hemophagocytic lymphohistiocytosis. Disruptive mutations and missense mutations with absent protein expression correlate with a younger onset age. Children with brainstem and cerebellitis patterns and a negative etiologic work-up require directed assessment for CNS hemophagocytic lymphohistiocytosis.

Ab-initio and experimental study of pentose sugar dehydration mechanism in the gas phase.

In this work pentose sugar (D-xylose, D-ribose and D-arabinose) gas phase dehydration reaction was investigated by means of mass spectrometric techniques and theoretical calculations. The ionic species derived from the dehydration reaction of protonated D-ribose and D-arabinose were structurally characterized by their fragmentation patterns and the relative dehydration energies measured by energy resolved CAD mass spectra. The results were compared with those recently obtained for D-xylose in the same mass spectrometric experimental conditions. Dehydration of C1-OH protonated sugars was theoretically investigated at the CCSD(T)/cc-pVTZ//M11/6-311++G(2d,2p) level of theory. Protonated pentoses are not stable and promptly lose a water molecule giving rise to the dehydrated ions at m/z 133. D-xylose, D-ribose and D-arabinose dehydration follows a common reaction pathway with ionic intermediates and transition states characterized by similar structures. Slightly different dehydration energies were experimentally measured and the relative trend was theoretically confirmed. The overall dehydration activation energy follows the order arabinose < ribose < xylose. Gas-phase pentose sugar dehydration leads to the formation of protonated 2-furaldehyde as final product. Based on the experimental and theoretical evidence a new mechanistic hypothesis starting from C1-OH protonation was proposed.

A new echo-Doppler method to measure interatrial conduction time. Validation and clinical usefulness.

AIM: The aim of this study was to assess if knowing the interatrial conduction time is useful to better program atrioventricular delay in sequential pacing. The study proposes a new echo-Doppler method to measure interatrial conduction time, correlating it with electrophysiological measures. METHODS: The new method was tested in 30 subjects who underwent electrophysiological study. Interatrial conduction time by new method was taken during atrial pacing as the interval between the artefact of electrocardiogram pacing, shown on screen echo, and the onset of the A wave of the echo-Doppler mitral inflow. The electrophysiological measures were obtained, in the same subjects and at the same time, by a decapolar catheter in coronary sinus as intervals between the artefact of atrial pacing and the first positive left atrial deflection at proximal (C7C8) and distal (C1C2) electrodes. RESULTS: Echo-Doppler mean time was 114±12 ms, electrophysiological time was 107±14 ms at C7C8 and 124±11 ms at C1C2. Statistical analysis showed a good correlation (r=0.92, P<0.001) and accord (mean difference=6.6 ms) between the two methods. CONCLUSION: The new method to measure interatrial conduction time is consistent with the electrophysiological method; it could be particularly useful in programming the best AV delay in sequential and biventricular pacing, to avoid atrial contraction against a closed mitral valve.

[Cardiac evaluation for non-cardiac surgical patients]. / Cardiac evaluation for non-cardiac surgical patients. sa.gre@ticali.it

There is no evidence that most of the clinical examinations we prescribe before any surgical operation may be useful to a prognostic evaluation of the patient. Recently, some authors showed that there was no postoperative difference between 2 groups of patients. The 1(st) group had performed many laboratory examinations, the 2(nd) group none at all. Both the surgical operations and the characteristics of the patients may foresee a high, intermediate or low risk. The major clinical complications may be foreseen through tested algorithms. Patients who are at risk of cardiac events should perform tests which may be invasive but may reveal a serious heart disease. In some cases, the patients should have to be submitted to heart surgery before their programmed intervention.

[Blood pressure self-monitoring]. / L'autorilievo della pressione arteriosa.

The blood pressure is measured, usually, in the last years by the patient at home. The method is useful for the screening of the true hypertensive patients, for the follow-up of "white coat" hypertension, for the control of antihypertensive therapy, and for the clinical trials. The home blood pressure is closer to real blood pressure of a subject and it is better correlated than clinical pressure to target organ damage. The normal values, 135/85 mmHg, are been established by meta-analysis studies. Automatic oscillometric devices should be used. The method, very useful in clinical practice, has to improve in accuracy and measures validation. Doctor has to spend more time to train the patient to use the devices correctly.

[Approach to the patient in vegetative state. Part II: differential diagnosis]. / Approccio al paziente in stato vegetativo. Parte II: La diagnosi differenziale.

A prerequisite to the diagnosis of vegetative state is the exclusion of apparently similar syndromes, in which the patient retains the consciousness partially or even completely. Some syndromes are not separate nosological entities and should be abandoned: the apallic state, the neocortical death, the decerebrate and decorticate state, the alpha-coma, the vigil or prolonged or irreversible coma are among them. Three conditions deserve special consideration. The term locked-in syndrome describes a patient completely paralysed and mute, but fully conscious, and is usually caused by ischemic lesions of the pons. Several variants do exist, either in the causes and site of lesion. Some patients may become paralysed and mute, but conscious because of polyneuropathies, that is in the absence of any lesions of the central nervous system. The akinetic mutism is a rare condition characterised by loss of speech and nearly absent bodily movements. Painful stimulation may cause appropriate withdrawing, and wakefulness and self-awareness may be preserved, but cognitive impairment is usually present. It must be emphasised that this condition can be due to potentially treatable lesions, such as hydrocephalus and craniopharyngioma. The term "minimally responsive" or "minimally conscious" describes severely disabled patients in whom meaningful responses can be demonstrated, although inconstantly. This condition, the true diagnostic challenge, often represents a transition phase of vegetative patients recovering consciousness. Physicians, physiotherapists and patient's relatives should work all together to reach a correct diagnosis, by using current available methods to monitorize the recovery of consciousness.

Olfaction in Parkinson's disease: methods of assessment and clinical relevance.

Several neurological conditions have been reported to be associated with peripheral or central deficits of olfactory system. In recent years particular emphasis has been placed on the early and severe olfactory impairment in Parkinson's disease (PD), in which limited neuropathological studies have revealed a marked dopaminergic deficit in the olfactory tubercles. Moreover, indirect evidence suggests that dysfunction of the dopaminergic pathways from mesencephalon to the piriform cortex may play a role in olfactory impairment in PD. A large number of clinical studies have reported that olfactory loss in idiopathic PD is bilateral, present in hemiparkinsonism, unrelated to the stage or clinical subtype of the disease, and independent of antiparkinsonian medication. In addition, major olfactory alterations have been reported in familial PD and dementia with Lewy bodies but not in progressive supranuclear palsy and essential tremor. These findings might stimulate further research targeted to determine the biological substrate of dissimilar olfactory performances in these movement disorders. The present review summarizes standardized procedures for the assessment of olfactory acuity (detection threshold), identification (multiple choice odor naming), discrimination (differentiation between similar/dissimilar odorants), and memory (recognition of a substance previously smelled). Specific suggestions concerning the psychometric and neuropsychological evaluation of PD patients are provided.

Spinal cord stimulation for the treatment of refractory angina pectoris: a two-year follow-up.

Twenty-three patients affected by severe, refractory angina were submitted to permanent spinal cord stimulation (SCS) and then followed in our outpatient clinic for 24 months. During the follow-up period, the number of weekly angina episodes drastically dropped from 9.2 (preimplant) to 1.8 in the 3rd, 2.5 in the 6th, 4.5 in the 12th, and 4.2 in the 24th month, with a statistically significant difference (P < 0.01) between the first and last values. A significant increase in the average exercise time from 320 +/- 120 seconds (in baseline condition) to 410 +/- 115 seconds (during SCS) was observed at the treadmill stress test (P < 0.01). SCS was well tolerated by all the patients. However, 7 patients died during follow-up (3 myocardial infarctions, 2 noncardiac deaths, and 2 sudden deaths). Three generators were replaced because of battery depletion after 15, 17, and 21 months. No serious complication was observed. In conclusion, in patients with otherwise intractable angina or already submitted to myocardial revascularization, SCS is very effective in reducing the number of angina episodes. The time of the work during exercise stress test is also significantly prolonged.

High prevalence of peripheral neuropathy in hepatitis C virus infected patients with symptomatic and asymptomatic cryoglobulinaemia.

BACKGROUND: Fifty per cent of patients with chronic hepatitis C, show detectable cryoglobulinaemia, even though most of them do not show cryoglobulinaemia related symptoms. Peripheral neuropathy is present in most of the patients with symptomatic cryoglobulinaemia, where it may be the first clinical manifestation. The prevalence of peripheral neuropathy in patients with hepatitis C and cryoglobulinaemia is unknown. AIMS: To assess the prevalence of peripheral neuropathy in HCV infected patients with symptomatic or asymptomatic detectable cryoglobulinaemia. PATIENTS AND METHODS: Eighty-nine patients with HCV infection and detectable cryoglobulinaemia underwent electrophysiological studies. RESULTS: Electrophysiological evidence of peripheral neuropathy was found in 37% and was significantly associated with: the presence of cryoglobulinaemia syndrome, older age, higher rheumatoid factor reactivity and immunoglobulin M levels and reduced complement C4 activity. However, electrophysiological evidence of peripheral neuropathy was unrelated to cryocrit levels and type of cryoglobulinaemia and was found in 23/68 patients without any symptoms of cryoglobulinaemia other than pain and paresthesia. CONCLUSIONS: These findings suggest that peripheral neuropathy is frequent in patients with hepatitis C and detectable cryoglobulins. Neuropathy was found to be present in 1/3 of patients without other cryoglobulinaemia-related symptoms, thus a direct or indirect role of HCV, independent of cryoglobulinaemia, in the pathogenesis of nerve damage cannot be ruled out.

Critical illness myopathy and neuropathy.

BACKGROUND: Critically ill patients may develop muscle weakness or paralysis during the course of sepsis and multiple-organ failure. We studied peripheral nerve and muscle disorders (NMD) in comatose patients. METHOD: Comatose patients who developed paralysis associated with absent deep-tendon reflexes had electroneuromyography (ENMG) and muscle-nerve biopsy specimens taken. Onset and duration of sepsis, multiple-organ dysfunction and failure, biochemical alterations, and drugs potentially interfering with nerve-muscle function were recorded. FINDINGS: 24 patients became quadriparetic or quadriplegic; muscle changes were found in 23. Axonal neuropathy was found in eight of 22 patients examined. All patients had prolonged sepsis and multiple-organ dysfunction, but only 14 had multiple-organ failure. Drugs such as steroids, neuromuscular-blocking agents, and aminoglycosides were not responsible for paresis, and the part played by hyperglycaemia and hypoalbuminaemia is uncertain. Attending physicians predicted a fatal outcome in all cases, although six of seven survivors fully recovered within 115-210 days from the onset of paralysis. INTERPRETATION: Comatose patients may become completely paralysed because of NMD. The diagnosis is important to avoid unnecessary investigations and unreasonably pessimistic prognosis. ENMG is essential for the diagnosis and for planning further clinical management. Biopsy needs to be done only when it is necessary to properly classify NMD.

Anterior corpus callosotomy: effects in a patient with congenital bilateral perisylvian syndrome and oromotor seizures.

Anterior corpus callosotomy was performed in a patient with pseudobulbar palsy, mild mental retardation and intractable epilepsy related to congenital bilateral perisylvian cortical dysplasia. Before surgery, she had daily atonic drop attacks, rare and mainly sleep-related oromotor seizures, and multifocal and diffuse paroxysmal EEG discharges; after callosotomy, less abrupt atonic drop attacks recurred monthly and the EEG epileptiform abnormalities disappeared. Video-EEG sleep recordings revealed the clinically unsuspected serial recurrence of oromotor seizures, probably related to the clinically observed aggravation of dysarthria. New surgical techniques, in addition or alternative to callosotomy, should be developed in order to avoid or reduce the risk of aggravating some types of partial seizures in patients with bilateral cortical displastic lesions, intractable epilepsy and epileptic falls.

Occipital lobe seizures related to clinically asymptomatic celiac disease in adulthood.

We report the electroclinical ictal findings of four epileptic patients with clinically asymptomatic celiac disease (CD). Celiac disease diagnosis was suspected by past history and/or computed tomography (CT) findings in all patients and confirmed by laboratory tests and jejunal biopsy. All patients had paroxysmal visual manifestations and ictal EEG discharges arising from the occipital lobe. Epilepsy evolution was favorable in two patients and severe in 2, regardless of CT evidence of occipital corticosubcortical calcifications in 2 patients. Occipital lobe seizures may be characteristic of the epilepsy related to CD, and epileptic patients with these seizures of unknown etiology should be carefully investigated for malabsorption. If past history and/or laboratory tests suggest gastrointestinal (GI) dysfunction they should also undergo small intestinal biopsy even if they do not have GI tract symptoms.

The effects of lengthening on nerves.

Use of external fixators in limb lengthening and skin expanders in plastic surgery are well-known operative techniques. In some cases neurologic complications arise due to distraction which is either excessive or too fast. What happens to the nerve in these cases has not yet been thoroughly investigated. We therefore conducted an experiment on the sciatic nerve of rats. In one group of animals the nerve was studied after lengthening the femur, and in the other group after lengthening the nerve itself with a skin expander. Electrophysiologic and histologic studies (optic microscopy and axon teasing) were used to examine the effects of tension on the sciatic nerve. The results suggest that if distraction is performed gradually, the nerve does not undergo any electrophysiologic functional changes. It does, however, undergo some morphologic changes, such as a decrease in both the areas of the axons and the myelin sheaths, an increase in the distances between the nodes, and proliferation of Schwann cells.

Monitoring of somatosensory evoked potentials during carotid endarterectomy: relationship with different haemodynamic parameters and clinical outcome.

The authors studied the changes of Somatosensory Evoked Potentials (SEPs) performed in 241 anaesthetised patients during 264 carotid endarterectomies (CEs). SEP responses were considered significantly modified when the central conduction time was greater than 1 ms and/or when the amplitude of the complex N20-P25 decreased by at least 50%. Both CCT and N20-P25 have been correlated with different parameters, including the presence or absence of preoperative neurological deficits, the type of general anaesthesia, the status of the contralateral and the ipsilateral carotid artery, stump pressure, the use of an intraluminal shunt and the perioperative results. After carotid cross-clamping SEP responses were within the normal range in 236 CEs (89%), and abnormal in 28 (11%). A shunt was inserted 23 times in 264 (9%) cases. None of the patients operated on in this series experienced a permanent neurological deficit; there were three (1.1%) transient deficits (two Rinds and one TIA) and two deaths from non-neurological causes. Only one of the transient deficits was present when the patient woke from the anaesthetic and this event was predicted by significant modification of the SEP which did not reverse after removal of the clamps (a shunt was not used). None of the patients in our series who did not present significant modifications of SEPs during the operation had any postoperative neurological deficit. The authors conclude that SEP recording is a highly reliable and objective method for continuous monitoring of brain function during CE.

Plasma amino acid patterns in experimental acute hepatic failure: comparison between hepatectomy and liver devascularization in pigs.

To clarify the physiopathologic mechanism leading to a marked increase in aromatic amino acids (AAA) in acute hepatic failure (AHF), we compared two experimental models of AHF. Ten pigs were submitted to one-stage hepatic devascularization (group A); in eight other pigs total hepatectomy was performed (group B). The animals were maintained under constant glucose infusion. The mean survival time in group A was 23 +/- 2 hours; after hepatectomy it was 30 +/- 4 hours. Hepatic coma progressively deepened from 8 +/- 3 hours in Group A animals and was delayed until 17 +/- 5 hours in the anhepatic pigs. AAA, methionine, and tryptophan immediately increased markedly in pigs with liver ischemia. In group B animals, AAA showed a slight increase only 18 hours after hepatectomy, whereas there were no significant differences in methionine and tryptophan. The different amino acid patterns in the two groups of animals demonstrate that hepatocyte necrosis is a major source of plasma amino acids after liver devascularization. The slight increase in AAA after total hepatectomy suggests that a release mechanism from muscular mass is involved in the later stages of the experiment. The onset of coma is related to the increase in AAA rather than to alterations in blood ammonia that did not differ in either group of animals.

[Angiographic control of portocaval anastomoses. A study of hepato-portal circulatory changes after shunt (author's transl)]. / Bilan angiographique des anastomoses porto-caves chirurgicales. Considérations sur les modifications circulatoires hépato-portales après dérivation.

The hepatoportal circulatory changes which occur after porto-systemic shunts have been evaluated in 55 cirrhotic patients studied by post-operative arterioportography. In every one of these cases the shunt was patent. After side to side portocaval shunt (28 patients) the arterioportography shows the complete drainage of the splanchnic blood into the inferior vena cava. A reversed flow was observed in 20 patients. After conventional spleno renal shunt (eight patients) a maintained hepatopetal flow was present only in early angiographic controls, while in later controls all splanchnic blood flow was towards the renal vein, with evidence of reversed portal flow. Even after mesocaval shunt (ten patients) the splanchnic flow was hepatofugal. Instead, after distal splenorenal Warren shunt (two cases) the hepatopetal portal flow seems to be unaffected as evidence by angiography 15 days post-operatively. An increased of the hepatic artery diameter and its intrahepatic branches was observed in 20 out of 27 controls. This hepatic artery "hepertrophy" is related in increased hepatic artery blood flow which seems to be, according to Burchell [5], an important factor in the reestablishment of the liver circulation after portocaval shunt.