Voices from the past: The pioneering use of the phonograph in neurology.

Since its discovery by the American inventor and industrialist Thomas Alva Edison (1847-1931) in 1877, the phonograph attracted much interest in the field of medicine. This article describes the earliest pioneering examples of the use of the phonograph in neurology. In France, the use of the phonograph for obtaining audio recordings of delusions and speech or language disturbances was first proposed by Victor Maurice Dupont (1857-1910) in 1889 and in Italy by the physician Gaetano Rummo (1853-1917), who had studied at La Salpêtrière under Jean-Martin Charcot (1825-1893). The applicability of the phonograph to the record of speech disturbances was illustrated in England by John Hughlings Jackson (1835-1911) and William Halse Rivers (1864-1922), and by William Hale White (1857-1949) and Cuthbert Hilton Golding-Bird (1848-1939) in 1891. Since then, audio recordings have been used rarely in neurology, a branch of medicine where the visual aspects dominate, to the extent that inspection can be enough to reach a definite clinical diagnosis. In the mid-20th century, the advent of audio and video recordings supplanted audio recordings alone, relegating them to a very marginal role.

Increased risk of epilepsy in patients registered in the Swedish Dementia Registry.

BACKGROUND AND PURPOSE: Data on epilepsy in dementia, particularly on its risk factors, are scarce. Confounding comorbidities and the rising incidence of epilepsy in older age have hampered studies in this field. The occurrence and risk factors for epilepsy in the Swedish Dementia Registry (SveDem), a large cohort of patients with dementia, have been examined. METHODS: Information on epilepsy and seizure-related diagnoses, comorbidities and survival were extracted for all individuals in SveDem (n = 81 192) and three randomly selected age- and gender-matched controls from the population register, excluding all with a dementia diagnosis (n = 223 933). The risk of epilepsy following dementia diagnosis was estimated with Kaplan-Meier curves, and Cox proportional hazard modelling was used to identify risk factors and adjust for comorbidities. RESULTS: A diagnosis of epilepsy was found more frequently amongst dementia patients [4.0%, 95% confidence interval (CI) 3.8-4.1] than controls (1.9%, 95% CI 1.9-2.0). The risk of incident epilepsy after dementia was 2.1% (95% CI 1.9-2.3) at 5 years and 4.0% (95%CI 3.4-4.6) at 10 years, compared to 0.8% (95% CI 0.8-0.8) and 1.6% (95% CI 1.4-1.8) respectively for controls. The risk was greatest for early-onset Alzheimer's disease. In multivariate analysis, dementia was associated with a hazard ratio of 2.52 (95% CI 2.31-2.74) for epilepsy. Young age, male sex, stroke, brain trauma, brain tumour and low Mini-Mental State Examination score significantly increased the risk. CONCLUSIONS: Dementia, particularly young-onset Alzheimer's disease, increases the risk of subsequent epilepsy. Further studies are needed to determine optimal management and the impact of epilepsy on prognosis.

A critical appraisal of randomized controlled trials on intravenous phenytoin in convulsive status epilepticus.

Since the 1970s, intravenous (IV) phenytoin (PHT) has traditionally been used as second-stage treatment for convulsive status epilepticus (SE) after failure of benzodiazepines. The aim of this review was to critically assess the evidence supporting the use of IV PHT as treatment of convulsive SE in patients of any age. In particular, we critically appraised the results of randomized controlled trials (RCTs) evaluating IV PHT as treatment of convulsive SE. A systematic search of the literature was carried out to identify RCTs evaluating IV PHT as treatment of convulsive SE in patients of any age. Eight RCTs (544 patients allocated to IV PHT) were included. The included studies differed in almost every single characteristic considered. Six RCTs (472 patients) used IV PHT without demonstrating refractoriness of SE to benzodiazepines. Only two RCTs (72 patients) used IV PHT as second-line treatment for benzodiazepine-resistant convulsive SE. Overall, most evidence from RCTs supports the use of IV PHT immediately after IV diazepam, even if seizures have not recurred. The recommendation derived from RCTs supporting the use of IV PHT as second-line treatment in benzodiazepine-resistant convulsive SE is weak. This is emblematic of the lack of robust evidence from large RCTs to inform clinical practice on how to treat SE after failure of first-line drugs. IV PHT given immediately after first-line benzodiazepines could prolong their short antiepileptic effect and prevent seizure recurrence.

Transcranial magnetic stimulation studies in complex regional pain syndrome type I: A review.

The sensory and motor cortical representation corresponding to the affected limb is altered in patients with complex regional pain syndrome (CRPS). Transcranial magnetic stimulation (TMS) represents a useful non-invasive approach for studying cortical physiology. If delivered repetitively, TMS can also modulate cortical excitability and induce long-lasting neuroplastic changes. In this review, we performed a systematic search of all studies using TMS to explore cortical excitability/plasticity and repetitive TMS (rTMS) for the treatment of CRPS. Literature searches were conducted using PubMed and EMBASE. We identified 8 articles matching the inclusion criteria. One hundred fourteen patients (76 females and 38 males) were included in these studies. Most of them have applied TMS in order to physiologically characterize CRPS type I. Changes in motor cortex excitability and brain mapping have been reported in CRPS-I patients. Sensory and motor hyperexcitability are in the most studies bilateral and likely involve corresponding regions within the central nervous system rather than the entire hemisphere. Conversely, sensorimotor integration and plasticity were found to be normal in CRPS-I. TMS examinations also revealed that the nature of motor dysfunction in CRPS-I patients differs from that observed in patients with functional movement disorders, limb immobilization, or idiopathic dystonia. TMS studies may thus lead to the implementation of correct rehabilitation strategies in CRPS-I patients. Two studies have begun to therapeutically use rTMS. This non-invasive brain stimulation technique could have therapeutic utility in CRPS, but further well-designed studies are needed to corroborate initial findings.

Low-frequency rTMS of the unaffected hemisphere in stroke patients: A systematic review.

The aim of this review was to summarize the evidence for the effectiveness of low-frequency (LF) repetitive transcranial magnetic stimulation (rTMS) over the unaffected hemisphere in promoting functional recovery after stroke. We performed a systematic search of the studies using LF-rTMS over the contralesional hemisphere in stroke patients and reviewed the 67 identified articles. The studies have been gathered together according to the time interval that had elapsed between the stroke onset and the beginning of the rTMS treatment. Inhibitory rTMS of the contralesional hemisphere can induce beneficial effects on stroke patients with motor impairment, spasticity, aphasia, hemispatial neglect and dysphagia, but the therapeutic clinical significance is unclear. We observed considerable heterogeneity across studies in the stimulation protocols. The use of different patient populations, regardless of lesion site and stroke aetiology, different stimulation parameters and outcome measures means that the studies are not readily comparable, and estimating real effectiveness or reproducibility is very difficult. It seems that careful experimental design is needed and it should consider patient selection aspects, rTMS parameters and clinical assessment tools. Consecutive sessions of rTMS, as well as the combination with conventional rehabilitation therapy, may increase the magnitude and duration of the beneficial effects. In an increasing number of studies, the patients have been enrolled early after stroke. The prolonged follow-up in these patients suggests that the effects of contralesional LF-rTMS can be long-lasting. However, physiological evidence indicating increased synaptic plasticity, and thus, a more favourable outcome, in the early enrolled patients, is still lacking. Carefully designed clinical trials designed are required to address this question. LF rTMS over unaffected hemisphere may have therapeutic utility, but the evidence is still preliminary and the findings need to be confirmed in further randomized controlled trials.

rTMS of the prefrontal cortex has analgesic effects on neuropathic pain in subjects with spinal cord injury.

STUDY DESIGN: Repetitive transcranial magnetic stimulation study. OBJECTIVES: The analgesic effects of repetitive transcranial magnetic stimulation (rTMS) in chronic pain have been the focus of several studies. In particular, rTMS of the premotor cortex/dorsolateral prefrontal cortex (PMC/DLPFC) changes pain perception in healthy subjects and has analgesic effects in acute postoperative pain, as well as in fibromyalgia patients. However, its effect on neuropathic pain in patients with traumatic spinal cord injury (SCI) has not been assessed. SETTING: Merano (Italy) and Salzburg (Austria). METHODS: In this study, we performed PMC/DLPFC rTMS in subjects with SCI and neuropathic pain. Twelve subjects with chronic cervical or thoracic SCI were randomized to receive 1250 pulses at 10 Hz rTMS (n=6) or sham rTMS (n=6) treatment for 10 sessions over 2 weeks. The visual analog scale, the sensory and affective pain rating indices of the McGill Pain Questionnaire (MPQ), the Hamilton Depression Rating Scale and the Hamilton Anxiety Rating Scale were used to assed pain and mood at baseline (T0), 1 day after the first week of treatment (T1), 1 day (T2), 1 week (T3) and 1 month (T4) after the last intervention. RESULTS: Subjects who received active rTMS had a statistically significant reduction in pain symptoms in comparison with their baseline pain, whereas sham rTMS participants had a non-significant change in daily pain from their baseline pain. CONCLUSION: The findings of this preliminary study in a small patient sample suggest that rTMS of the PMC/DLPFC may be effective in relieving neuropathic pain in SCI patients.

The contribution of neurophysiology in the diagnosis and management of cervical spondylotic myelopathy: a review.

STUDY DESIGN: Topical review of the literature. OBJECTIVE: The objective of this review article was to assess indications and usefulness of various neurophysiological techniques in diagnosis and management of cervical spondylogenic myelopathy (CSM). METHODS: The MEDLINE, accessed by Pubmed and EMBASE electronic databases, was searched using the medical subject headings: 'compressive myelopathy', 'cervical spondylotic myelopathy (CSM)', 'cervical spondylogenic myelopathy', 'motor evoked potentials (MEPs)', 'transcranial magnetic stimulation', 'somatosensory evoked potentials (SEPs)', 'electromyography (EMG)', 'nerve conduction studies (NCS)' and 'cutaneous silent period (CSP)'. RESULTS: SEPs and MEPs recording can usefully supplement clinical examination and neuroimaging findings in assessing the spinal cord injury level and severity. Segmental cervical cord dysfunction can be revealed by an abnormal spinal N13 response, whereas the P14 potential is a reliable marker of dorsal column impairment. MEPs may also help in the differential diagnosis between spinal cord compression and neurodegenerative disorders. SEPs and MEPs are also useful in follow-up evaluation of sensory and motor function during surgical treatment and rehabilitation. EMG and NCS improve the sensitivity of cervical radiculopathy detection and may help rule out peripheral nerve problems that can cause symptoms that are similar to those of CSM. CSP also shows a high sensitivity for detecting CSM. CONCLUSION: Neuroimaging, especially magnetic resonance imaging, represents the procedure of choice for the diagnosis of CSM, but a correct interpretation of morphological findings can be achieved only if they are correlated with functional data. The studies reported in this review highlight the crucial role of the electrophysiological studies in diagnosis and management of CSM.

Assessment of corticospinal excitability after traumatic spinal cord injury using MEP recruitment curves: a preliminary TMS study.

STUDY DESIGN: Transcranial magnetic stimulation study. OBJECTIVES: To further investigate the corticospinal excitability changes after spinal cord injury (SCI), as assessed by means of transcranial magnetic stimulation (TMS). SETTING: Merano (Italy) and Salzburg (Austria). METHODS: We studied resting motor threshold (RMT), motor evoked potential (MEP) amplitude and recruitment curve in five subjects with good recovery after traumatic incomplete cervical SCI. RESULTS: RMT did not differ significantly between patients and controls, whereas the slope of MEP recruitment curve was significantly increased in the patients. CONCLUSION: This abnormal finding may represent an adaptive response after SCI. The impaired ability of the motor cortex to generate proper voluntary movement may be compensated by increasing spinal excitability. The easily performed measurement of MEP recruitment curve may provide a useful additional tool to improve the assessment and monitoring of motor cortical function in subjects with SCI. Increasing our knowledge of the corticospinal excitability changes in the functional recovery after SCI may also support the development of effective therapeutic strategies.

[¹²³I]FP-CIT SPECT (DaTSCAN) may be a useful tool to differentiate between Parkinson's disease and vascular or drug-induced parkinsonisms: a meta-analysis.

BACKGROUND AND PURPOSE: Differentiating idiopathic Parkinson's disease from secondary parkinsonian syndromes is crucial since their management and prognosis differ considerably. Functional imaging of the dopaminergic pathway by means of [¹²³I]FP-CIT SPECT (DaTSCAN) might be useful in this regard, but its role is still controversial. The accuracy of DaTSCAN in the differential diagnosis between Parkinson's disease and vascular or drug-induced parkinsonism was therefore systematically reviewed. METHODS: MEDLINE and CENTRAL were searched for studies aiming to determine accuracy measures (sensitivity, specificity, diagnostic odds ratio, positive and negative likelihood ratios) of DaTSCAN in differentiating between Parkinson's disease and vascular or drug-induced parkinsonism. RESULTS: Five studies were included. Pooled accuracy measures in differentiating between Parkinson's disease and vascular or drug-induced parkinsonism were relatively high, with sensitivity and specificity values above 85% and 80%, respectively. CONCLUSIONS: DaTSCAN might accurately differentiate between early Parkinson's disease and secondary parkinsonian conditions, namely vascular or drug-induced, in patients with clinically unclear parkinsonism. However, all the studies reviewed here show several methodological limits, which prevent definitive conclusions on the role of DaTSCAN being drawn in this context. Further studies are needed to confirm our results and definitely evaluate the utility of DaTSCAN in differentiating between Parkinson's disease and vascular or drug-induced parkinsonism.

Transcranial magnetic stimulation (TMS)/repetitive TMS in mild cognitive impairment and Alzheimer's disease.

Several Transcranial Magnetic Stimulation (TMS) techniques can be applied to noninvasively measure cortical excitability and brain plasticity in humans. TMS has been used to assess neuroplastic changes in Alzheimer's disease (AD), corroborating findings that cortical physiology is altered in AD due to the underlying neurodegenerative process. In fact, many TMS studies have provided physiological evidence of abnormalities in cortical excitability, connectivity, and plasticity in patients with AD. Moreover, the combination of TMS with other neurophysiological techniques, such as high-density electroencephalography (EEG), makes it possible to study local and network cortical plasticity directly. Interestingly, several TMS studies revealed abnormalities in patients with early AD and even with mild cognitive impairment (MCI), thus enabling early identification of subjects in whom the cholinergic degeneration has occurred. Furthermore, TMS can influence brain function if delivered repetitively; repetitive TMS (rTMS) is capable of modulating cortical excitability and inducing long-lasting neuroplastic changes. Preliminary findings have suggested that rTMS can enhance performances on several cognitive functions impaired in AD and MCI. However, further well-controlled studies with appropriate methodology in larger patient cohorts are needed to replicate and extend the initial findings. The purpose of this paper was to provide an updated and comprehensive systematic review of the studies that have employed TMS/rTMS in patients with MCI and AD.

rTMS modulates reciprocal inhibition in patients with traumatic spinal cord injury.

STUDY DESIGN: Randomized, double-blind, crossover, sham-controlled trial. OBJECTIVES: Repetitive transcranial magnetic stimulation (rTMS) over the primary motor cortex (M1) leads to a significant reduction of spasticity in subjects with spinal cord injury (SCI), but the physiological basis of this effect is still not well understood. The purpose of this study was to evaluate the disynaptic reciprocal Ia inhibition of soleus motoneurons in SCI patients. SETTING: Department of Neurology, Merano, Italy and TMS Laboratory, Paracelsus Medical University, Salzburg, Austria. METHODS: Nine subjects with incomplete cervical or thoracic SCI received 5 days of daily sessions of real or sham rTMS applied over the contralateral M1. We compared the reciprocal inhibition, the Modified Ashworth Scale and the Spinal Cord Injury Assessment Tool for Spasticity at baseline, after the last session and 1 week later in the real rTMS and sham stimulation groups. RESULTS: We found that real rTMS significantly reduced lower limb spasticity and restored the impaired excitability in the disynaptic reciprocal inhibitory pathway. CONCLUSIONS: In a small proof-of-concept study, rTMS strengthened descending projections between the motor cortex and inhibitory spinal interneuronal circuits. This reversed a defect in reciprocal inhibition after SCI, and reduced leg spasticity.

Central motor conduction studies in patients with spinal cord disorders: a review.

STUDY DESIGN: Topical review of the literature. OBJECTIVES: The evaluation of patients with myelopathies requires radiological investigations; however, for the correct interpretation of the neuroimaging findings, the functional assessment of corticospinal conduction is helpful or even mandatory in many conditions. The objective of this review article was to assess the utility of the motor evoked potentials (MEPs) in diagnosis and management of the most frequent spinal cord disorders. SETTING: Salzburg (Austria) and Merano (Italy). METHODS: A MEDLINE search was performed using following terms: 'motor evoked potentials', 'transcranial magnetic stimulation', 'central motor conduction', 'compressive myelopathy', 'spinal cord infarction', 'spinal cord injury', 'syringomyelia', 'myelitis', 'hereditary spastic paraparesis', 'subacute combined degeneration' and 'hepatic myelopathy'. RESULTS: Central motor conduction abnormalities can be detected also in the absence of neuroradiological abnormalities-for example, in patients with subacute combined degeneration or hepatic myelopathy. In the most frequent patients with compressive myelopathies, MEPs were found to be very helpful in determining the functional significance of neuroimaging findings. MEP recording can supplement clinical examination and neuroimaging findings also in the assessment of the spinal cord injury level. In patients with spinal cord infarction, the MEP study can demonstrate spinal involvement even when radiological evidence for spinal cord damage is absent or equivocal, thus allowing an important early diagnosis. CONCLUSION: MEPs represent a highly sensitive and accurate diagnostic tool in many different spinal cord disorders. MEPs can also be useful in follow-up evaluation of motor function during treatment and rehabilitation.

Central motor and sensory conduction in patients with hepatic myelopathy.

STUDY DESIGN: Experimental neurophysiological study. OBJECTIVES: The hepatic myelopathy (HM) is characterized by progressive weakness and spasticity of the lower extremities, while there are only a few reports of sensory impairment. However, sensory function has been poorly explored in HM. We believe that an electrophysiological assessment of dorsal columns by somatosensory evoked potentials (SEPs) and of cortico-spinal lateral tracts by motor evoked potentials (MEPs) should be of considerable value in the functional evaluation of the spinal cord involvement in patients with HM. SETTING: Salzburg (Austria) and Merano (Italy). METHODS: Eight patients diagnosed with HM were studied with MEPs and SEPs. Neurological examination revealed different degrees of cortico-spinal tract involvement in all patients and sensory abnormalities in three patients. RESULTS: Central motor conduction to lower limb muscles was abnormal in all patients, while central sensory conduction was abnormal in seven out of the eight patients. Both central motor and sensory conduction to upper limbs are normal in all patients. CONCLUSION: The main finding is that electrophysiological evidence of central sensory involvement is present in a very high percentage of patients with HM, and that the threshold for electrophysiological abnormalities is below that for clinical manifestations. Therefore, central sensory and motor conduction studies are sensitive methods for detecting, localizing and monitoring spinal cord damage in HM.

Aristotle - Ἀριστοτέλης (ARISTOTÉLES, 384/3- 322/1 BCE) The revelation of tuberculosis in his zoological works.

One of the most challenging issues with the sources of ancient medicine is to be able to identify the correspondence between the diseases we know today and those reported in ancient medical texts. Ancient diseases' definitions rarely help us, and the symptoms described often correspond to more than one disease. This is especially true about tuberculosis, a disease that historians of medicine habitually associates with the Greek words phthi(n)o (φθίνω), verb, phthisis/phthoe (φθίσις/φθόη), noun, phthinodes/phthisikos (φθινώδης/φθισικός), adjective, all etymologically linked to an Indo-European root that expresses the idea of consumption in a broad sense. This article aims to analyze a group of Greek words, branchos/branchia (ßράγχος/ßράγχια), krauros/kraurao (κραῦρος/κραυράω), and katarreo (καταρρέω), that appear in nosological contexts very close to the infectious disease that today we call tuberculosis. Moreover, the paper aims to focus on the transmission pathways of TB being via animal-human contact and some ancient strategies to cure it. The symptoms, transmission pathways and therapeutic approach of tuberculosis belong to a homogeneous pathological picture that emerges from a set of texts that date back to the period between the fifth century BC and the second century AD.

Progesterone and its derivatives for the treatment of catamenial epilepsy: A systematic review.

OBJECTIVE: Catamenial epilepsy (CE) is defined as an increase in seizure frequency during specific phases of the menstrual cycle in women with epilepsy. The treatment usually includes a combination of non-hormonal and hormonal therapies. This systematic review summarizes the available data on the efficacy of progesterone and its derivates to treat CE. METHODS: We performed a systematic search of the literature to identify studies reporting data on the use of progesterone and its derivatives (any type and dose) for the treatment of CE. The main outcome included the efficacy of progesterone and its derivatives on seizure frequency. RESULTS: Nineteen articles (457 patients) were included; four were randomized controlled trials (two comparing progesterone vs placebo and two comparing norethisterone vs placebo). Progesterone was generally administered during the luteal phase (from day 15 to 25) or during perimenstrual exacerbations (from day 23 to 25), with an average dose of 10-30 mg/day to a maximum of 300 mg/day. The therapy, usually well tolerated, was ineffective in the randomized controlled trials; conversely, it was associated with an overall reduction in seizure frequency in case reports and uncontrolled studies. CONCLUSIONS: Although data from uncontrolled studies suggest that hormone therapy with progesterone may be useful in the treatment of CE, its efficacy has not been demonstrated in controlled trials. The possible antiseizure effect of progesterone could be mediated by its active metabolite allopregnanolone, making the plasmatic measurement of these hormones mandatory to evaluate efficacy. Further randomized controlled trials should investigate the efficacy of progesterone and its derivatives, addressing these pharmacological issues.

IV Valproate in generalized convulsive status epilepticus: a systematic review.

Aim of this review was to evaluate efficacy and safety of intravenous valproate (IV VPA) in the treatment of generalized convulsive status epilepticus (GCSE) in patients of any age, synthesizing available evidences from randomized controlled trials (RCTs). RCTs on IV VPA administered in patients (no age restriction) for GCSE at any stage were searched in MEDLINE, EMBASE and Cochrane Central Register of Controlled Trials. Studies were selected and data independently extracted. Following outcomes were considered: clinical seizure cessation after drug administration, seizure freedom at 24 h, and adverse effects. Outcomes were assessed using standard methods to calculate risk ratio (RR) with 95% confidence intervals. Five trials met inclusion criteria. Two different comparisons were available (IV VPA versus phenytoin (PHT), IV VPA versus IV Diazepam), but only the former included more than one study with enough information to permit a meta-analysis. Compared with PHT, VPA had statistically lower risk of adverse effects (RR 0.31, 95% CI 0.12-0.85), with no differences in GCSE cessation after drug administration (RR 1.31, 95% CI 0.93-1.84) and in seizure freedom at 24 h (RR 0.96, 95% CI 0.88-1.06). This review suggests that IV VPA has a better tolerability than PHT in treatment of GCSE, without any statistically significant differences in terms of efficacy. More rigorous RCTs of VPA versus an appropriate comparator, in a well-defined population with a systematic definition of SE, are however required to conclude about efficacy and tolerability of VPA in clinical practice.

Digital therapeutics in neurology.

Digital therapeutics (DTx) is a section of digital health defined by the DTx Alliance as "delivering evidence-based therapeutic interventions to patients that are driven by software to prevent, manage, or treat a medical disorder or disease. They are used independently or in concert with medications, devices, or other therapies to optimize patient care and health outcomes". Chronic disabling diseases could greatly benefit from DTx. In this narrative review, we provide an overview of DTx in the care of patients with neurological dysfunctions.