The Italian technical/administrative recommendations for telemedicine in clinical neurophysiology.

Recent advances in technology, information technology, Internet networks, and, more recently, fiber optics in industrialized countries allow the exchange of a huge amount of data, in real time, across the globe. The acquisition of increasingly sophisticated technologies has made it possible to develop telemedicine, by which the specialist's evaluation can be carried out on the patient even remotely. In Italy, this very useful tool, although possible from a technological and information technology point of view, has not been developed because of the lack of clear and univocal rules and of major administrative obstacles related to the Italian Public Health System. To promote telemedicine implementation in Italy, the Italian Society of Clinical Neurophysiology and the Italian Society of Telemedicine together with the National Centre for Telemedicine and New Assistive Technologies of the Italian Higher Institute of Health prepared these inter-society recommendations. Because of potential forensic value of these recommendations, they were prepared considering the current regulations and the General Data Protection Regulation and will provide the basis for a Consensus Conference planned to discuss and prepare National Telemedicine Guidelines.

Why we prefer levetiracetam over phenytoin for treatment of status epilepticus.

Over last fifty years, intravenous (iv) phenytoin (PHT) loading dose has been the treatment of choice for patients with benzodiazepine-resistant convulsive status epilepticus and several guidelines recommended this treatment regimen with simultaneous iv diazepam. Clinical studies have never shown a better efficacy of PHT over other antiepileptic drugs. In addition, iv PHT loading dose is a complex and time-consuming procedure which may expose patients to several risks, such as local cutaneous reactions (purple glove syndrome), severe hypotension and cardiac arrhythmias up to ventricular fibrillation and death, and increased risk of severe allergic reactions. A further disadvantage of PHT is that it is a strong enzymatic inducer and it may make ineffective several drugs that need to be used simultaneously with antiepileptic treatment. In patients with a benzodiazepine-resistant status epilepticus, we suggest iv administration of levetiracetam as soon as possible. If levetiracetam would be ineffective, a further antiepileptic drug among those currently available for iv use (valproate, lacosamide, or phenytoin) can be added before starting third line treatment.

Neurophysiological prediction of neurological good and poor outcome in post-anoxic coma.

OBJECTIVE: Investigation of the utility of association between electroencephalogram (EEG) and somatosensory-evoked potentials (SEPs) for the prediction of neurological outcome in comatose patients resuscitated after cardiac arrest (CA) treated with therapeutic hypothermia, according to different recording times after CA. METHODS: Glasgow Coma Scale, EEG and SEPs performed at 12, 24 and 48-72 h after CA were assessed in 200 patients. Outcome was evaluated by Cerebral Performance Category 6 months after CA. RESULTS: Within 12 h after CA, grade 1 EEG predicted good outcome and bilaterally absent (BA) SEPs predicted poor outcome. Because grade 1 EEG and BA-SEPs were never found in the same patient, the recording of both EEG and SEPs allows us to correctly prognosticate a greater number of patients with respect to the use of a single test within 12 h after CA. At 48-72 h after CA, both grade 2 EEG and BA-SEPs predicted poor outcome with FPR=0.0%. When these neurophysiological patterns are both present in the same patient, they confirm and strengthen their prognostic value, but because they also occurred independently in eight patients, poor outcome is predictable in a greater number of patients. SIGNIFICANCE: The combination of EEG/SEP findings allows prediction of good and poor outcome (within 12 h after CA) and of poor outcome (after 48-72 h). Recording of EEG and SEPs in the same patients allows always an increase in the number of cases correctly classified, and an increase of the reliability of prognostication in a single patient due to concordance of patterns.

Single electroencephalographic patterns as specific and time-dependent indicators of good and poor outcome after cardiac arrest.

OBJECTIVE: To evaluate the prognostic value of single EEG patterns recorded at various time-frames in postanoxic comatose patients. METHODS: This retrospective study included 30-min EEGs, classified according to the definitions of continuity of background activity given by the American Clinical Neurophysiology Society. Isoelectric pattern was distinguished from other suppressed activities. Epileptiform patterns were considered separately. Outcome was dichotomised based on recovery of consciousness as good (Glasgow Outcome Scale [GOS] 3-5) or poor (GOS 1-2). RESULTS: We analysed 211 EEGs, categorised according to time since cardiac arrest (within 12h and around 24, 48 and 72h). In each time-frame we observed at least one EEG pattern which was 100% specific to poor or good outcome: at 12h continuous and nearly continuous patterns predicted good outcome and isoelectric pattern poor outcome; at 24h isoelectric and burst-suppression predicted poor outcome; at 48 and 72h isoelectric, burst-suppression and suppression (2-10µV) patterns predicted poor outcome. CONCLUSIONS: The prognostic value of single EEG patterns, defined according to continuity and voltage of background activity, changes until 48-72h after cardiac arrest and in each time-frame there is at least one pattern which accurately predicts good or poor outcome. SIGNIFICANCE: Standard EEG can provide time-dependent reliable indicators of good and poor outcome throughout the first 48-72h after cardiac arrest.

Absent SEP during therapeutic hypothermia did not reappear after re-warming in comatose patients following cardiac arrest.

BACKGROUND: Early prediction of neurological outcome for patients resuscitated from cardiac arrest (CA) is a challenging task. Therapeutic hypothermia (TH) has been shown to improve neurological outcome after CA. Two recent studies indicated that somatosensory evoked potentials (SEP) recorded during TH retains high prediction value for poor neurological outcome. It remains unclear whether TH can influence the recovery of bilaterally absent (BA) N20 after re-warming. The primary endpoint of the present study was to evaluate if patients with BA SEPs during TH can recover cortical responses after re-warming. The secondary endpoint was to evaluate whether BA SEPs recorded during TH retains its prediction value for poor neurological outcome as in normothermic patients. METHODS: A single centre prospective cohort study including comatose adults resuscitated from in/out-of-hospital CA treated with TH. SEPs were recorded during TH (6-24 hours after CA) and after re-warming in those patients who remained comatose. Neurological outcome was assessed 6 months after CA using the Glasgow Outcome Scale. RESULTS: Sixty patients were included. In patients with preserved SEP, no significant differences were found between N20 mean amplitude during TH and after re-warming. During TH, 24 patients showed bilaterally absent N20 but none of these recovered cortical responses after re-warming. All patients with absent SEPs during TH did not recover consciousness. CONCLUSIONS: In a single centre cohort of comatose CA patients, our results showed that all patients with absent SEPs during early recording (6-24 hours) during TH showed bilaterally absent SEPs after re-warming. As a secondary result we confirmed previous data that BA SEPs during TH retains its prognostic value for poor neurological outcome, as in normothermic patients.

Neurophysiological monitoring in adult and pediatric intensive care.

Clinical neurophysiology is both an extension of clinical examination and an integration of neuroimaging. It plays a role in diagnosis, prognosis and monitoring in the Intensive Care Unit (ICU). Electroencephalography (EEG) and somatosensory evoked potentials (SEPs) are the most informative neurophysiological tests. Both have a major prognostic role in the hypoxic-ischemic encephalopathy and traumatic brain injury (TBI). In the former the absence of bilateral cortical SEPs has an unfavorable prognostic significance of 100%, whereas bilateral normal SEPs has uncertain prognostic value. In TBI these SEP patterns have high early prognostic value for both bad and good outcome. Continuous EEG monitoring is indicated for diagnosis and treatment of non convulsive seizures and status epilepticus (NCSE), whereas SEPs are more able to indicate the occurrence of neurological deterioration. In our opinion EEG-SEP monitoring is also valuable for interpretation and management of ICP trends, contributing to optimise treatment in a single patient. The EEG seems to have the same prognostic utility in pediatric as in adult ICU. Recent reviews supported the use of SEPs in the integrated process of outcome prediction after acute brain injury in children. However differences in interpretation are needed and the issue is whether it is possible to establish an age limit over which the prediction of SEPs is similar to that in adults. There are only a few studies of seizure prevalence in pediatric ICU. The variability of frequency of NCSE in comatose children is high as in adults and, similar to the adult, remains unclear the impact on outcome.

Consensus on the use of neurophysiological tests in the intensive care unit (ICU): electroencephalogram (EEG), evoked potentials (EP), and electroneuromyography (ENMG).

STUDY AIM: To provide a consensus of European leading authorities about the optimal use of clinical neurophysiological (CN) tests (electroencephalogram [EEG]; evoked potentials [EP]; electroneuromyography [ENMG]) in the intensive care unit (ICU) and, particularly, about the way to make these tests clinically useful for the management of individual patients. METHODS: This study gathered together several European clinical neurophysiologists and neurointensivists whose leading contributions in the adult or paediatric ICU and in continuous neuromonitoring had been peer-acknowledged. It was based on both a literature review and each participant's own experience. Given the methodological impossibility to gather studies fulfilling criteria of evidence-based medicine, this article essentially relies on expert opinions that were gained after several rounds, in which each expert was invited to communicate his own contribution to all other experts. A complete consensus has been reached when submitting the manuscript. RESULTS: What the group considered as the best classification systems for EEG and EP abnormalities in the ICU is first presented. CN tests are useful for diagnosis (epilepsy, brain death, and neuromuscular disorders), prognosis (anoxic ischemic encephalopathy, head trauma, and neurologic disturbances of metabolic and toxic origin), and follow-up, in the adult, paediatric, and neonatal ICU. Regarding prognosis, a clear distinction is made between these tests whose abnormalities are indicative of an ominous prognosis and those whose relative normalcy is indicative of a good prognosis. The prognostic significance of any test may vary as a function of coma etiology. CONCLUSION: CN provides quantitative functional assessment of the nervous system. It can be used in sedated or curarized patients. Therefore, it should play a major role in the individual assessment of ICU patients.

Continuous EEG-SEP monitoring in severe brain injury.

AIMS: To monitor acute brain injury in the neurological intensive care unit (NICU), we used EEG and somatosensory evoked potentials (SEP) in combination to achieve more accuracy in detecting brain function deterioration. METHODS: Sixty-eight patients (head trauma and intracranial hemorrhage; GCS<9) were monitored with continuous EEG-SEP and intracranial pressure monitoring (ICP). RESULTS: Fifty-five patients were considered "stable" or improving, considering the GCS and CT scan: in this group, SEP didn't show significant changes. Thirteen patients showed neurological deteriorations and, in all patients, cortical SEP showed significant alterations (amplitude decrease>50% often till complete disappearance). SEP deterioration anticipated ICP increase in 30%, was contemporary in 38%, and followed ICP increase in 23%. Considering SEP and ICP in relation to clinical course, all patients but one with ICP less than 20 mmHg were stable, while the three patients with ICP greater than 40 mmHg all died. Among the 26 patients with ICP of 20-40 mmHg, 17 were stable, while nine showed clinical and neurophysiological deterioration. Thus, there is a range of ICP values (20-40 mmHg) were ICP is scarcely indicative of clinical deterioration, rather it is the SEP changes that identify brain function deterioration. Therefore, SEP have a twofold interest with respect to ICP: their changes can precede an ICP increase and they can constitute a complementary tool to interpret ICP trends. It has been very important to associate SEP and EEG: about 60% of our patients were deeply sedated and, because of their relative insensitivity to anesthetics, only SEP allowed us to monitor brain damage evolution when EEG was scarcely valuable. CONCLUSIONS: We observed 3% of nonconvulsive status epilepticus compared to 18% of neurological deterioration. If the aim of neurophysiological monitoring is to "detect and protect", it may not be limited to detecting seizures, rather it should be able to identify brain deterioration, so we propose the combined monitoring of EEG with SEP.

Transient post-traumatic locked-in syndrome: a case report and a literature review.

INTRODUCTION: Post-traumatic locked-in syndrome may be particularly difficult to recognize, especially when it follows a state of coma and presents the clinical feature of a "total" locked-in syndrome. PATIENT AND METHODS: A 56-year-old male with a closed head injury was admitted in intensive care unit (ICU) with GCS=4 (V1, M2, E1). Computed tomography (CT) scan disclosed a limited subarachnoid haemorrhage in the sylvian region without any brain oedema or ventricular shift. The GCS did not change until day 6. At the same time EEG showed a reactivity to acoustic stimuli consisting in the paradoxical appearance of a posterior rhythm in alpha range (10-12c/s), blocked by passive eye opening. Early cortical components (N20-P25) of somatosensory evoked potentials were normal on both hemispheres; middle components were also clearly evident. Magnetic resonance imaging of the brain showed both diffuse and midbrain axonal injuries, particularly in a strategic lesion involving both cerebral peduncles. Event related potentials showed N2 and P3 components to stimulation by rare tones. CONCLUSIONS: A comprehensive multimodal neurophysiological approach, using the more informative tests and the proper time of recording, should be included in protocols for patients with severe head trauma, in order to establish the actual patient's clinical state and to avoid that a locked-in syndrome state be mistaken for prolonged coma, vegetative state, minimally conscious state or akinetic mutism. Neurophysiological evaluation before discharge from ICU can be a baseline evaluation useful for the follow-up of low-responsive patients in the neuro-rehabilitation unit.

Evoked potentials in the ICU.

The most informative neurophysiological techniques available in the neurosurgical intensive care unit are electroencephalograph and somatosensory evoked potentials. Such tools, which give an evaluation of cerebral function in comatose patients, support clinical evaluation and are complementary to neuroimaging. They serve both diagnostic/prognostic and monitoring purposes. While for the former, discontinuous monitoring is sufficient, for the latter, to obtain increased clinical impact, continuous monitoring is necessary. To perform and interpret these examinations in the neurosurgical intensive care unit, both the technician and the neurophysiologist need specific training in the intensive care field. There is sufficient evidence to show that somatosensory evoked potentials are the best single indicator of early prognosis in traumatic and hypoxic-ischaemic coma compared to the Glasgow Coma Score, computed tomography scan and electroencephalograph. Indeed, somatosensory evoked potentials should always be combined with clinical examination to determine the prognosis of coma. Despite widespread use of somatosensory evoked potentials and their prognostic utility in acute brain injury, few studies exist on continuous somatosensory evoked potential monitoring in the intensive care unit. We carried out a pilot study of continuous electroencephalograph-somatosensory evoked potential monitoring in the neurosurgical intensive care unit (traumatic brain injury and intracranial haemorrhage, Glasgow Coma Score <9, intracranial pressure monitoring). All patients stable from a clinical and computed tomography scan point of view showed no significant somatosensory evoked potential modifications, while in the case of clinical deterioration (23%), somatosensory evoked potentials always showed significant modifications. While somatosensory evoked potentials correlated with short-term outcome, intracranial pressure showed a poor correlation. We believe neurophysiological monitoring is an ideal complement to the other parameters monitored in the neurosurgical intensive care unit. Whereas intracranial pressure is simply a pressure index, electroencephalograph-somatosensory evoked potential monitoring reflects to what extent cerebral parenchyma still remains metabolically active during acute brain injury.

Continuous EEG-SEP monitoring of severely brain injured patients in NICU: methods and feasibility.

AIMS: To evaluate the feasibility of a continuous neurophysiologic monitoring (electroencephalography (EEG)-somatosensory evoked potentials (SEPs)) in the neuro-intensive care unit (NICU), taking into account both the technical and medical aspects that are specific of this environment. METHODS: We used an extension of the recording software that is routinely used in our unit of clinical neurophysiology. It performs cycles of alternate EEG and SEP recordings. Raw traces and trends are simultaneously displayed. Patient head and stimulator box are placed behind the bed and linked to the ICU monitoring terminal through optic fibers. The NICU staff has been trained to note directly clinical events, main artefacts and therapeutic changes. The hospital local area network (LAN) enables remote monitoring survey. RESULTS: Continuous EEG (CEEG)-SEP monitoring was performed in 44 patients. Problems of needle detachment were seldomly encountered, thanks to the use of a sterile plastic dressing, which covers needles. We never had infection or skin lesions due to needles or the electrical stimulator. The frequent administration of sedative at high doses prevented us from having a clinically valuable EEG in several cases but SEPs were always monitorable, independently of the level of EEG suppression. The diagnosis of seizures and non-epileptic status was based on raw EEG, while quantitative EEG (QEEG) was used to quantify ictal activity as a guide to treatment. CONCLUSIONS: EEG and EP waveforms collected in NICU were of comparable quality to routine clinical measurements and contained the same clinical information. A continuous SEP monitoring in a comatose and sedated patient in NICU is not technically more difficult and potentially less useful than in operating room. This monitoring appears to be feasible provided the observance of some requirement regarding setting, electrodes, montages, personnel integration, consulting and software.

Anti-ganglioside antibodies and elevated CSF IgG levels in Guillain-Barré syndrome.

Anti-ganglioside antibody production and dysfunction of blood-cerebrospinal fluid (CSF) barrier (BCB) are frequent findings in dysimmune neuropathy patients, whereas intrathecal synthesis of immunoglobulins is still a matter of debate. We examined the CSF, immunological and electrophysiological characteristics from a cohort of patients with Guillain-Barré syndrome (GBS) and chronic inflammatory demyelinating polyneuropathy (CIDP), and from patients with other neurological diseases as control. Thirty-eight percent of GBS patients and 28% of CIDP patients had detectable serum titers of anti-ganglioside antibodies, which were associated with a high incidence of motor conduction block and increased F wave latencies. In GBS patients, but not in CIDP or control patients, there was an association between anti-ganglioside antibodies and increased CSF immunoglobulin-G (IgG) levels as determined by the IgG index. However, none of the GBS patients had CSF oligoclonal bands (OBs) or indications of intrathecal anti-ganglioside antibody synthesis. The possibility of an abnormal CSF concentration of immunoglobulins from serum through dysfunctional BCB or damaged nerve roots, and the role of serum anti-ganglioside reactivity in this process are discussed.

Anoxic-ischemic alpha coma: prognostic significance of the incomplete variant.

The prognostic significance of post-anoxic-ischemic alpha coma (AC) is controversial. We recorded somatosensory evoked potentials (SEPs) and performed serial electroencephalography (EEG) in a 60-year-old woman in coma after cardiac arrest. The first EEG was recorded after 48 hours (GCS=5; E1-V1-M3); brain-stem reflexes were preserved. The EEG pattern showed monotonous alpha frequencies (10-11 Hz) with posterior predominance; acoustic and noxious stimuli evoked EEG reactivity. Early cortical SEPs (72 h) were normal. On the fifth day (GCS=8; E4-V1-M3), the EEG alpha pattern was replaced by a diffuse delta activity; rhythmic theta changes appeared spontaneously or in response to stimuli. The patient regained consciousness on the tenth day and EEG showed posterior theta activity (6-7 c/s) partially reactive to stimuli. At the 6-month follow-up, cognitive evaluation showed mild dementia. Recent studies identified two forms of AC. Patients with complete AC have an outcome that is almost invariably poor. Conversely, incomplete AC (posteriorly accentuated alpha frequency, reactive and with SEPs mostly normal) reflects a less severe degree of anoxic-ischemic encephalopathy. The case we report should be classified, according to the SEPs and EEG features, as incomplete AC. The fact that the patient has regained consciousness, even if with residual cognitive impairment, confirms the need to distinguish this variant from complete AC.

Idiopatic spinal cord herniation: a treatable cause of Brown-Séquard syndrome.

We report two cases of thoracic idiopathic spinal cord herniation (ISCH) focusing on the peculiar diagnostic and therapeutic issues posed by this rare disorder. In particular MR evaluation of CSF dynamic with a 2D PC cine-MR technique and demonstration of progressive cord herniation on consecutive MR examinations allowed insight on the differential diagnosis and pathophysiological mechanisms of ISCH.

Assessment of trigeminal small-fiber function: brain and reflex responses evoked by CO2-laser stimulation.

Laser pulses selectively excite mechano-thermal nociceptors and evoke brain potentials that may reveal small-fiber dysfunction. We applied CO2-laser pulses to the perioral and supraorbital regions and recorded the scalp laser-evoked potentials (LEPs) and reflex responses in the orbicularis oculi, masticatory, and neck muscles in 30 controls and 10 patients with facial sensory disturbances. Low-intensity pulses readily evoked scalp potentials consisting of a negative component with a latency of 165 ms followed by a positive component at 250 ms. In vertex recordings, the amplitude of LEPs exceeded 30 microV. Although only high-intensity pulses evoked reflex responses, some subjects showed--even to low-intensity pulses--an orbicularis oculi (blink-like) response that markedly contaminated the scalp recording. Scalp LEPs were abnormal in patients with hypalgesia and normal trigeminal reflexes and normal in patients with normal pain sensitivity and abnormal trigeminal reflexes. Possibly because of the high receptor density in this area and the short conduction distance, laser stimulation of the trigeminal territory yields low-threshold and large LEPs, which are useful for detecting dysfunction in peripheral and central pain pathways.

Fatal herpesvirus 6 encephalitis after unrelated bone marrow transplant.

A complex pattern of neurological dysfunctions with generalized seizures and visual allucinations, but without focal signs, suddenly arose 20 days after an unrelated bone marrow transplant for chronic myelogenous leukemia (CML) in a 13-year-old girl, accompanied by signs of acute skin graft-versus-host disease (GVHD). Magnetic resonance imaging (MRI) revealed multiple bilateral foci of signal abnormalities, which were exclusively localized in the grey matter, sparing the white. Extensive microbiological and virological assays of cerebrospinal fluid (CSF) allowed the identification of HHV-6, variant A, DNA. Further progression of both neurological alterations and of skin and gut GVHD led to a fatal outcome 2 weeks later. A retrospective analysis of both the recipient and donor mononuclear cell suspensions supported the hypothesis that HHV-6 had been acquired from the donor with the bone marrow graft. This report suggests a pathogenetic role of HHV-6 in viral encephalitis in immunocompromised bone marrow transplant (BMT) recipients, and its possible association with GVHD.

Familial AL-amyloidosis in three Italian siblings.

BACKGROUND AND METHODS: Familial occurrence of immunoglobulin-related (AL) amyloidosis has occasionally been reported. In this work we describe the concomitance of systemic amyloidosis and monoclonal gammopathy (one case of Waldenström's macroglobulinemia and two cases without multiple myeloma or related diseases) in three Italian siblings, two males and one female. RESULTS AND CONCLUSIONS: All of them showed a common pattern of polyneuropathy to different degrees; two presented a sicca syndrome and one also suffered from nephropathy. Two of them showed the same HLA typing with the same light chain type (k), but had different presenting symptoms. Polyneuropathy and a history of peptic disease in two cases was suggestive of type III familial amyloidotic polyneuropathy (FAP) occurring in the setting of a familial monoclonal component. However, immunohistochemical studies on different tissue specimens using anti-apolipoprotein A1 and anti-transthyretin antibodies were negative. Further screening of DNA samples for transthyretin (TTR) gene mutations was also negative. Clinical and laboratory investigations ruled out reactive or senile amyloidosis and immunohistochemical studies with anti-light chain antibodies on amyloidotic tissue specimens were positive. As a consequence, this family represents a new case of familial AL-amyloidosis.

[99mTc HMPAO (technetium 99m-hexamethylpropyleneamine oxime) angioscintigraphy in the diagnosis of brain death]. / Angioscintigrafia con 99mTc HMPAO (Technetium 99m-Hexametyl propilene amino oxime) nella diagnosi di morte cerebrale.

The diagnosis of brain death has great importance for the social and medical purposes, such as organs transplantation, and is based on clinical examination and EEG records. We report two doubtful cases of brain death in whom the 99mTc HMPAO scintigraphy was used to confirm the complete absence of cerebral perfusion.

"Epilepsia partialis continua" due to multifocal encephalitis: favourable outcome after immunoglobulin treatment.

The case of a young woman with EPCK is described in which neoplastic and vascular disorders were excluded. Supported by EEG and PET, EPCK was imputed to multifocal encephalitis notwithstanding serological and CSF negativity. Cerebral biopsy confirmed the inflammatory nature of the affection, although the etiologic agent was not identified. High dose intravenous immunoglobulin therapy was followed by the prompt disappearance of EPCK and the remission of the other neurological deficits.