Temporal lobe epilepsy (TLE) is the most prevalent form of complex partial seizures with temporal lobe origin of electrical abnormality. Studies have shown that recurrent seizures affect all aspects of cognitive functioning, including memory, language, praxis, executive functions, and social judgment, among several others. In this article, we will review these cognitive impairments along with their neuropathological correlates in a comprehensive manner. We will see that neuropsychological deficits are prevalent in TLE. Much of the effort has been laid on memory due to the notion that temporal lobe brain structures involved in TLE play a central role in consolidating information into memory. It seems that damage to the mesial structure of the temporal lobe, particularly the amygdale and hippocampus, has the main role in these memory difficulties and the neurobiological plausibility of the role of the temporal lobe in different aspects of memory. Here, we will cover the sub-domains of working memory and episodic memory deficits. This is we will further proceed to evaluate the evidences of executive function deficits in TLE and will see that set-shifting among other EFs is specifically affected in TLE as is social cognition. Finally, critical components of language related deficits are also found in the form of word-finding difficulties. To conclude, TLE affects several of cognitive function domains, but the etiopathogenesis of all these dysfunctions remain elusive. Further well-designed studies are needed for a better understanding of these disorders.
Neuropsychological deficits; temporal lobe epilepsy; neurological correlates
The ketogenic diet is a high-fat, low-carbohydrate, and restricted protein diet that is useful in patients with refractory epilepsy. The efficacy of the ketogenic diet is better than most of the new antiepileptic drugs. Other modifications of the diet are also beneficial, such as the modified Atkins diet and the low glycemic index treatment. There is a lack of awareness of the ketogenic diet as a treatment modality for epilepsy amongst pediatricians and neurologists. In this review, the use of the ketogenic diet and other dietary treatments in refractory epilepsy is discussed. The Indian experience with the use of these dietary treatments is also briefly reviewed.
Infantile spasms; intractable epilepsy; ketogenic diet; the modified Atkins diet
Ever since Kiloh (1961) coined the term pseudo-dementia, it has been used a little loosely for describing the cognitive deficits in depression, especially, which is found in old age. However, several diagnostic dilemmas persist regarding the nosological status of this condition. Teasing out these individual diagnostic problems is important not only for administering appropriate therapy, but also for preventing them from the unnecessary diagnostic assessments towards the other diagnoses. Thus, it is important to have a detailed knowledge of the cognitive or neuropsychological deficits in this condition. In this review, we start by addressing the important issue of diagnostic confusion between dementia and pseudo-dementia. Subsequently, we proceed by reviewing the present scientific literature on the cognitive deficits found in this clinical condition. For the sake of convenience, we will divide the cognitive deficits into:
Memory deficitsExecutive function deficits andDeficits in speech and language domains.
Finally, we will look at the progression of this condition to see the components of this condition, which can be actually called “Pseudo”.
Cognition; executive functions; memory; pseudodementia
Stroke is a major health problem world-wide and its burden has been rising in last few decades. Until now tissue plasminogen activator is only approved treatment for stroke. Angiogenesis plays a vital role for striatal neurogenesis after stroke. Administration of various growth factors in an early post ischemic phase, stimulate both angiogenesis and neurogenesis and lead to improved functional recovery after stroke. However vascular endothelial growth factors (VEGF) is the most potent angiogenic factor for neurovascularization and neurogenesis in ischemic injury can be modulated in different ways and thus can be used as therapy in stroke. In response to the ischemic injury VEGF is released by endothelial cells through natural mechanism and leads to angiogenesis and vascularization. This release can also be up regulated by exogenous administration of Mesenchymal stem cells, by various physical therapy regimes and electroacupuncture, which further potentiate the efficacy of VEGF as therapy in post stroke recovery. Recent published literature was searched using PubMed and Google for the article reporting on methods of up regulation of VEGF and therapeutic potential of growth factors in stroke.
Angiogenesis; ischemic stroke; vascular endothelial growth factors
Dementia is a chronic neurodegenerative disorder characterized by progressive cognitive loss. Alzheimer's disease (AD) and the Lewy body disease are the two most common causes of age-related degenerative dementia. Visuo-cognitive skills are a combination of very different cognitive functions being performed by the visual system. These skills are impaired in both AD and dementia with Lewy bodies (DLB). The aim of this review is to evaluate various studies for these visuo-cognitive skills. An exhaustive internet search of all relevant medical databases was carried out using a series of key-word applications, including The Cochrane Library, MEDLINE, PSYCHINFO, EMBASE, CINAHL, AMED, SportDiscus, Science Citation Index, Index to Theses, ZETOC, PEDro and occupational therapy (OT) seeker and OT search. We reviewed all the articles until March 2013 with key words of: Visual skills visual cognition dementia AD, but the direct neurobiological etiology is difficult to establish., Dementia of Lewy body disease. Although most studies have used different tests for studying these abilities, in general, these tests evaluated the individual's ability of (1) visual recognition, (2) visual discrimination, (3) visual attention and (4) visuo-perceptive integration. Performance on various tests has been evaluated for assessing these skills. Most studies assessing such skills show that these skills are impaired in DLB as compared with AD. Visuo-cognitive skills are impaired more in DLB as compared with AD. These impairments have evident neuropathological correlations, but the direct neurobiological etiology is difficult to establish.
Alzheimer's disease; Lewy body disease; visuo-cognitive skills
Rising stroke and higher mortality among Indian population needs focused attention for prevention and early management of stroke. In India, very few studies have been carried out to determine the causes of deficiencies in knowledge, attitude and practice (KAP) of stroke among Indians. Study on KAP is essential to improve the awareness about stroke, early diagnosis and institution of appropriate management. In this article, we have reviewed the existing literature on this issue and tried to compare it with those of developed countries and suggested the measures we need to adopt in India to improve awareness and knowledge base.
Awareness; risk factors; prevention strategies; stroke; India
Recent histological studies of thrombi retrieved from patients with an acute ischemic stroke using the endovascular thrombectomy devices and correlation with early vessel computed tomography (CT) and magnetic resonance imaging (MRI) characteristics have given relevant insights into the pathophysiology of thrombotic lesions and may facilitate the development of improved reperfusion treatment approaches. We present a review of recent studies on the histopathologic analysis of thrombi, studies of MRI, and CT imaging correlation with thrombus histology, and detailed structural analysis of thromboemboli retrieved by thrombectomy devices during an acute ischemic stroke.
Clot composition; histopathology; stroke; thrombus
The dominantly inherited ataxias, also known as Spino-cerebellar ataxias (SCAs), are rapidly expanding entities. New mutations are being identified at remarkable regularity. Recent awareness of molecular abnormalities in SCAs has addressed some of the long sought questions, but gaps in knowledge still exist. Three major categories of SCAs, according to molecular mechanisms, have evolved over recent few years: Polyglutamate expansion ataxia, non-coding zone repeat ataxia, and ataxia due to conventional mutation. Using the fulcrum of these mechanisms, the article provides an update of SCAs. Shared and specific clinical features, genetic abnormalities, and possible links between molecular abnormalities and cerebellar degeneration have been discussed. Emphasis has been placed on the mechanisms of polyglutamate toxicity.
Autosomal dominant cerebellar ataxia; polyglutamate; spino-cerebellar ataxia
The cornerstone of diagnosis of Alzheimer's disease (AD) is still the clinical criteria for probable and possible AD established by the NINCDS-ADRDA Work Group in 1984, which had survived for over 27 years. However, with the increase in people's knowledge of clinical manifestations and biology of AD, this standard is gradually proving to be insufficient; the early diagnosis of AD is thus particularly important. Therefore, in 2011, the National Institute on Aging and the Alzheimer's Association revised the criteria and integrated biomarker evidence into it. Biomarker evidence is expected to enhance the pathophysiological specificity of the diagnosis of AD. According to Consensus Report of the Working Group on Molecular and Biochemical Markers of Alzheimer's Disease, a qualified biomarker for AD should have the following abilities: It should detect a fundamental feature of neuropathology and be validated in neuropathologically confirmed cases, reliably with an sensitivity >80% for detecting AD and a specificity >80% for distinguishing other dementias; be reproducible and non-invasive; and be simple to perform and inexpensive. Alzheimer-associated neuronal thread protein (AD7c-NTP) is a member of “neuronal thread proteins” (NTPs); it can be detected in increased concentration in cortical neurons, brain-tissue extracts, cerebrospinal fluid, and urine in the early course of AD neurodegeneration, and it level is proportional to the degree of dementia, which makes it a promising biomarker for AD. In this review, we have evaluated the feasibility of developing AD7c-NTP as a biomarker for AD.
AD7c-NTP; Alzheimer's disease; biomarker; brain tissue extracts; cortical neurons; CSF; urine
Mild cognitive impairment (MCI) is associated with an increased risk of developing dementia. This is clinically relevant overt dementia can be prevented if treatment strategies are devised for MCI. Neuropsychological deficits in this condition are very common and are important clinically for treatment and outcomes. We aimed to review various neuropsychological deficits in MCI. Further, we have presented the current evidence for nosological status, neuroanatomical basis, and clinical outcome of this heterogeneous construct. All published papers on the topic of neuropsychological deficits in MCI on Medline and other databases were reviewed. A wide range of memory and executive function deficits are common in MCI patients. However, several studies are limited by either improper designs or inadequate sample sizes. Several neuropsychological impairments like memory function and executive functions can be diagnosed in MCI. The evidence base for the exact neuroanatomical basis of MCI is not robust yet. However, given the wide range of outcomes, controversies and debates exist regarding the nosological significance of the deficits. Hence, more studies are needed to specifically locate the impairments and further delineate the construct of MCI.
Cognition; dementia; mild cognitive impairment
The reported prevalence of cognitive deficits within the first month of stroke ranges widely from 10% to 82%, depending primarily on the criteria used to define cognitive impairment and on the selected patient population. These cognitive defects progress toward impairment over a course of time if left untreated. Among the most common cognitive deficits are the attentional, the visuoperceptual, the memory and executive function deficits. As these impairments are being increasingly recognized in the scientific communities, more and more studies are being devoted to the outcomes of various therapies for these disorders. In this review, we focus on the outcomes of various therapies for these cognitive disorders over time. We reviewed all the possible medical databases using key words for individual cognitive deficit treatment outcomes. All the possible studies including randomized controlled trials, pre-post design studies, case series and single case reports were included in this study. On the basis of present literature review, we conclude that the evidence is definitively positive only for outcomes of attentional and visuoperceptive skill deficits. On the other hand, there have been very few studies to conclude for effectiveness of various therapies for memory and executive function outcomes.
Cognition; interventions; neuropsychological outcome; stroke
Analgesia and sedation has been widely used in intensive care units where iatrogenic discomfort often complicates patient management. In neurological patients maximal comfort without diminishing patient responsiveness is desirable. In these patients successful management of sedation and analgesia incorporates a patient based approach that includes detection and management of predisposing and causative factors, including delirium, monitoring using sedation scales, proper medication selection, emphasis on analgesia based drugs and incorporation of protocols or algorithms. So, to optimize care clinician should be familiar with the pharmacokinetic and pharmacodynamic variables that can affect the safety and efficacy of analgesics and sedatives.
Analgesia; neurocritical care; sedation
Glossopharyngeal neuralgia is a relatively rare condition characterized by severe, paroxysmal episodes of pain localized to the external ear canal, the base of the tongue, the tonsil or the area beneath the angle of the jaw. This pain is many a times confused with Trigeminal Neuralgia and mistreated. There are various diagnostic and management dilemmas which are herein addressed in this review.
Glossopharyngeal neuralgia; glossopharyngeal neuralgia; stylalgia
This review is on ultrastructure and subcellular physiology at normal and abnormal neuromuscular junctions. The clinical and electrophysiological findings in myasthenia gravis, Lambert-Eaton myasthenic syndrome (LEMS), congenital myasthenic syndromes, and botulinum intoxication are discussed. Single fiber electromyography (SFEMG) helps to explain the basis of testing neuromuscular junction function by repetitive nerve stimulation (RNS). SFEMG requires skill and patience and its availability is limited to a few centers. For RNS supramaximal stimulation is essential and so is display of the whole waveform of each muscle response at maximum amplitude. The amplitudes of the negative phase of the first and fourth responses are measured from baseline to negative peak, and the percent change of the fourth response compared with the first represents the decrement or increment. A decrement greater than 10% is accepted as abnormal and smooth progression of response amplitude train and reproducibility form the crux. In suspected LEMS the effect of fast rates of stimulation should be determined after RNS response to slow rates of stimulation. Caution is required to avoid misinterpretation of potentiation and pseudofacilitation.
Acetylcholine; congenital myasthenic syndromes; Lambert–Eaton myasthenic syndrome; myasthenia gravis; repetitive nerve stimulation; single-fiber electromyography
Hippocampus is a complex brain structure embedded deep into temporal lobe. It has a major role in learning and memory. It is a plastic and vulnerable structure that gets damaged by a variety of stimuli. Studies have shown that it also gets affected in a variety of neurological and psychiatric disorders. In last decade or so, lot has been learnt about conditions that affect hippocampus and produce changes ranging from molecules to morphology. Progresses in radiological delineation, electrophysiology, and histochemical characterization have made it possible to study this archicerebral structure in greater detail. Present paper attempts to give an overview of hippocampus, both in health and diseases.
AD; atrophy; drug target; early Alzheimer's; hippocampus; hippocampal atrophy; prevention
The ancient mind and body healing methods of yoga recently sparked fervor in the scientific community as an alternative and complementary means of therapy. Since the World Health Organization officially began promoting yoga in developing countries in 1978, yoga has been cited for its therapeutic potential and has been widely recognized in Western culture. However, as an increasing number of people practice yoga for remedial purposes, researchers raise two important questions: 1) Is yoga a valid complementary management and rehabilitation treatment modality? 2) What conditions show promise of treatment with this intervention?.
This review article uses comprehensive scientific, evidence-based studies to analyze the efficacy of various basic and applied aspects of yoga in disease prevention and health promotion. It specifically intends to expose the effects of yoga in neurological disorders, particularly epilepsy, stroke, multiple sclerosis, Alzheimer's disease, peripheral nervous system disease, and fibromyalgia.
Materials and Methods:
Information was gathered from various resources including PubMed, Ovid, MD-Consult, USC, and U.C.L.A. libraries. Studies were selected and reviewed on the basis of sample size, control, randomization, double-blinding, and statistical analysis of results.
The pratice of yoga and meditation demonstrates statistically encouraging physiological and psychological improvements in the aforementioned neurological disorders. However, there were certain flaws and inadequacies in the study designs employed to evaluate the same. A critical analysis of these studies is presented.
With the aim to focus attention on this widespread yet largely unexamined treatment modality, this paper seeks to provide direction and support for further research necessary to validate yoga as an integrative, alternative, and complementary therapy.
Neurology; physiology and treatments; yoga
It is important to recognise that migraine is a ‘biological’ and not a ‘psychological’ entity. However, psychological factors can be involved in migraine in 4 different ways:- 1) Migraines can be triggered by psychological stressors; 2) Severe migraine can itself be a cause of significant psychological stress which can, in turn, exacerbate the problem; 3) Even if psychological stress is not significantly involved in the genesis of the headache, pain management techniques can help people cope with their pain more effectively; 4) Longitudinal data demonstrate a complex bidirectional association between mood disorders and migraine. Treatment of a co-existing mood disorder, for example with cognitive behavioural techniques, may therefore reduce the impact of migraine. It would thus appear logical to view medical and psychological approaches as potentially synergistic rather than mutually exclusive. Functional imaging indicates that cognition, emotions, and pain experiences change the way the brain processes pain inputs. This may provide a physiological rationale for psychological interventions in pain management. As most studies of psychological management of migraine have been relatively small and the approach often varies between clinicians, the magnitude of benefit, optimum method of delivery, and the length of intervention are uncertain.
Cognitive behavioural therapy; migraine; psychological; psychology
Chronic Daily Headache is a descriptive term that includes disorders with headaches on more days than not and affects 4% of the general population. The condition has a debilitating effect on individuals and society through direct cost to healthcare and indirectly to the economy in general. To successfully manage chronic daily headache syndromes it is important to exclude secondary causes with comprehensive history and relevant investigations; identify risk factors that predict its development and recognise its sub-types to appropriately manage the condition. Chronic migraine, chronic tension-type headache, new daily persistent headache and medication overuse headache accounts for the vast majority of chronic daily headaches. The scope of this article is to review the primary headache disorders. Secondary headaches are not discussed except medication overuse headache that often accompanies primary headache disorders. The article critically reviews the literature on the current understanding of daily headache disorders focusing in particular on recent developments in the treatment of frequent headaches.
Chronic daily headache; chronic migraine; chronic tension type headache; hemicrania continua; new daily persistent headache
The ‘Other Primary Headaches’ include eight recognised benign headache disorders. Primary stabbing headache is a generally benign disorder which often co-exists with other primary headache disorders such as migraine and cluster headache. Primary cough headache is headache precipitated by valsalva; secondary cough has been reported particularly in association with posterior fossa pathology. Primary exertional headache can occur with sudden or gradual onset during, or immediately after, exercise. Similarly headache associated with sexual activity can occur with gradual evolution or sudden onset. Secondary headache is more likely with both exertional and sexual headache of sudden onset. Sudden onset headache, with maximum intensity reached within a minute, is termed thunderclap headache. A benign form of thunderclap headache exists. However, isolated primary and secondary thunderclap headache cannot be clinically differentiated. Therefore all headache of thunderclap onset should be investigated. The primary forms of the aforementioned paroxysmal headaches appear to be Indomethacin sensitive disorders. Hypnic headache is a rare disorder which is termed ‘alarm clock headache’, exclusively waking patients from sleep. The disorder can be Indomethacin responsive, but can also respond to Lithium and caffeine. New daily persistent headache is a rare and often intractable headache which starts one day and persists daily thereafter for at least 3 months. The clinical syndrome more often has migrainous features or is otherwise has a chronic tension-type headache phenotype. Management is that of the clinical syndrome. Hemicrania continua straddles the disorders of migraine and the trigeminal autonomic cephalalgias and is not dealt with in this review.
Cough headache; exertional headache; hypnic headache; primary headache disorders; stabbing headache
Episodic migraine is a common debilitating condition with significant worldwide impact. An effective management plan must include acute treatment to relieve the pain and potential disability associated with the attacks and may also include preventative treatments with an aim of decreasing attack frequency and severity in the longer term. Acute treatments must be limited to a maximum of 2-3 days a week to prevent medication overuse headache and focus on simple analgesia, non-steroidal anti-inflammatory drugs and triptans. Preventative treatments are numerous and should be considered when migraine attacks are frequent and or disabling, acute medication is failing, in special circumstances such as hemiplegic migraines or if the patient requests them. All preventative medications must be given at therapeutic doses for at least 6-8 weeks before an adequate trial can be judged ineffective. The most important factor in choosing drugs is the patient and the clinical features of their attack and treatment should be tailored to these. Relative co-morbidities will influence drug choice, as will the side effect profile and the efficacy of the drug. First line preventative drugs include ß-blockers, amitriptyline and anti-epileptic drugs such as topiramate and valproate. Drugs with lower efficacy or poorer side effect profiles include selective serotonin reuptake inhibitors (SSRIs), calcium channel antagonists, gabapentin and herbal medicines.
Acute; migraine; preventative; prophylaxis; treatment
The trigeminal autonomic cephalalgias (TACs) are a group of primary headache disorders that are characterized by strictly unilateral trigeminal distribution pain occurring in association with ipsilateral cranial autonomic symptoms. This group includes cluster headache, paroxysmal hemicrania and short-lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing. These disorders are very painful, often considered to be some of the most painful conditions known to mankind, and consequently are highly disabling. They are distinguished by the frequency of attacks of pain, the length of the attacks and very characteristic responses to medical therapy, such that the diagnosis can usually be made clinically, which is important because it dictates therapy. The management of TACs can be very rewarding for physicians and highly beneficial to patients.
Cluster headache; paroxysmal hemicrania; SUNA; SUNCT; trigeminal autonomic cephalalgias
Evidence is emerging that migraine is not solely a headache disorder. Observations that ischemic stroke could occur in the setting of a migraine attack, and that migraine headaches could be precipitated by cerebral ischemia, initially highlighted a possibly association between migraine and cerebrovascular disease. More recently, large population-based studies that have demonstrated that migraineurs are at increased risk of stroke outside the setting of a migraine attack have prompted the concept that migraine and cerebrovascular disease are comorbid conditions. Explanations for this association are numerous and widely debated, particularly as the comorbid association does not appear to be confined to the cerebral circulation as cardiovascular and peripheral vascular disease also appear to be comorbid with migraine. A growing body of evidence has also suggested that migraineurs are more likely to be obese, hypertensive, hyperlipidemic and have impaired insulin sensitivity, all features of the metabolic syndrome. The comorbid association between migraine and cerebrovascular disease may consequently be explained by migraineurs having the metabolic syndrome and consequently being at increased risk of cerebrovascular disease. This review will summarise the salient evidence suggesting a comorbid association between migraine, cerebrovascular disease and the metabolic syndrome.
Comorbidities; metabolic syndrome; migraine; obesity; stroke
New daily persistent headache (NDPH) is a chronic headache developing in a person who does not have a past history of headaches. The headache begins acutely and reaches its peak within 3 days. It is important to exclude secondary causes, particularly headaches due to alterations in cerebrospinal fluid (CSF) pressure and volume. A significant proportion of NDPH sufferers may have intractable headaches that are refractory to treatment. The condition is best viewed as a syndrome rather than a diagnosis. The headache can mimic chronic migraine and chronic tension-type headache, and it is also important to exclude secondary causes, particularly headaches due to alterations in CSF pressure and volume. A large proportion of NDPH sufferers have migrainous features to their headache and should be managed with treatments used for treating migraine. A small group of NDPH sufferers may have intractable headaches that are refractory to treatment.
Chronic daily headache; new daily persistent headache; intractable headache
Headache is very common. In the United Kingdom, it accounts for 4.4% of primary care consultations, 30% of referrals to neurology services and 0.5–0.8% of alert patients presenting to emergency departments. Primary headache disorders account for the majority of patients and most patients do not require investigation. Warning features (red flags) in the history and on examination help target those who need investigation and what investigations are required. This article summarizes the typical presentations of the common secondary headaches and what neuroimaging and other investigations are appropriate for each headache type.
Intracranial hypotension; lumbar puncture; neuroimaging; raised intracranial pressure; thunderclap headache
Tension type headaches are common in clinical practice. Earlier known by various names, the diagnosis has had psychological connotations. Recent evidence has helped clarify the neurobiological basis and the disorder is increasingly considered more in the preview of neurologists. The classification, clinical features, differential diagnosis and treatment of tension type headache are discussed in this paper.
Episodic tension type headache; Chronic tension type headache