Hippocampal sclerosis (HS) or mesial temporal sclerosis (MTS) is a neuropathological condition with severe neuronal cell loss and

gliosis Gliosis is a nonspecific reactive change of glial cells in response to damage to the central nervous system (CNS). In most cases, gliosis involves the proliferation or hypertrophy of several different types of glial cells, including astrocytes, ...

in the

hippocampus The hippocampus (via Latin from Greek , 'seahorse') is a major component of the brain of humans and other vertebrates. Humans and other mammals have two hippocampi, one in each side of the brain. The hippocampus is part of the limbic system, a ...

, specifically in the CA-1 (Cornu Ammonis area 1) and

subiculum The subiculum (Latin for "support") is the most inferior component of the hippocampal formation. It lies between the entorhinal cortex and the CA1 subfield of the hippocampus proper. The subicular complex comprises a set of related structures in ...

of the hippocampus. It was first described in 1880 by Wilhelm Sommer. Hippocampal sclerosis is a frequent pathologic finding in community-based

dementia Dementia is a disorder which manifests as a set of related symptoms, which usually surfaces when the brain is damaged by injury or disease. The symptoms involve progressive impairments in memory, thinking, and behavior, which negatively affe ...

. Hippocampal sclerosis can be detected with autopsy or

MRI Magnetic resonance imaging (MRI) is a medical imaging technique used in radiology to form pictures of the anatomy and the physiological processes of the body. MRI scanners use strong magnetic fields, magnetic field gradients, and radio waves ...

. In MRI, a decrease in signal is observed at T1 and an increase in signal at T2.

Positron emission tomography Positron emission tomography (PET) is a functional imaging technique that uses radioactive substances known as radiotracers to visualize and measure changes in Metabolism, metabolic processes, and in other physiological activities including bl ...

is also used as an aid for diagnosis. In

PET A pet, or companion animal, is an animal kept primarily for a person's company or entertainment rather than as a working animal, livestock, or a laboratory animal. Popular pets are often considered to have attractive appearances, intelligence, ...

examination, glucose uptake is lower than in the normal part. The reason for this is that the sclerotic part works at a lower level than the normal part and needs less energy. Individuals with hippocampal sclerosis have similar initial symptoms and rates of dementia progression to those with

Alzheimer's disease Alzheimer's disease (AD) is a neurodegeneration, neurodegenerative disease that usually starts slowly and progressively worsens. It is the cause of 60–70% of cases of dementia. The most common early symptom is difficulty in short-term me ...

(AD) and therefore are frequently misclassified as having Alzheimer's Disease. But clinical and pathologic findings suggest that hippocampal sclerosis has characteristics of a progressive disorder although the underlying cause remains elusive. A diagnosis of hippocampal sclerosis has a significant effect on the life of patients because of the notable mortality,

morbidity A disease is a particular abnormal condition that negatively affects the structure or function of all or part of an organism, and that is not immediately due to any external injury. Diseases are often known to be medical conditions that a ...

and social impact related to

epilepsy Epilepsy is a group of non-communicable neurological disorders characterized by recurrent epileptic seizures. Epileptic seizures can vary from brief and nearly undetectable periods to long periods of vigorous shaking due to abnormal electrical ...

, as well as side effects associated with antiepileptic treatments. Findings indicate that there is a strong genetic connection in the development of mesial temporal sclerosis. Mesial temporal sclerosis used to be most commonly found as a single lesion in the brains of chronic epileptics who died a natural death which was estimated to be developed as a result of continued febrile convulsions.

Symptoms and signs

Histopathological Histopathology (compound of three Greek words: ''histos'' "tissue", πάθος ''pathos'' "suffering", and -λογία ''-logia'' "study of") refers to the microscopic examination of tissue in order to study the manifestations of disease. Spec ...

hallmarks of hippocampal sclerosis include segmental loss of

pyramidal neurons Pyramidal cells, or pyramidal neurons, are a type of multipolar neuron found in areas of the brain including the cerebral cortex, the hippocampus, and the amygdala. Pyramidal neurons are the primary excitation units of the mammalian prefrontal cor ...

granule cell A granule is a large particle or grain. It can refer to: * Granule (cell biology), any of several submicroscopic structures, some with explicable origins, others noted only as cell type-specific features of unknown function ** Azurophilic granul ...

dispersion Dispersion may refer to: Economics and finance *Dispersion (finance), a measure for the statistical distribution of portfolio returns *Price dispersion, a variation in prices across sellers of the same item *Wage dispersion, the amount of variatio ...

and reactive gliosis. This means that pyramidal neuronal cells are lost, granule cells are spread widely or driven off, and glial cells are changed in response to damage to the central nervous system (CNS). Generally, hippocampal sclerosis may be seen in some cases of epilepsy, particularly temporal lobe epilepsy. It is important to clarify the nature of insults that most likely have caused the hippocampal sclerosis and have initiated the epileptogenic process. Presence of hippocampal sclerosis and duration of epilepsy longer than 10 years were found to cause

parasympathetic The parasympathetic nervous system (PSNS) is one of the three divisions of the autonomic nervous system, the others being the sympathetic nervous system and the enteric nervous system. The enteric nervous system is sometimes considered part of t ...

autonomic dysfunction, whereas seizure refractoriness was found to cause sympathetic autonomic dysfunction. Apart from its association with the chronic nature of epilepsy, hippocampal sclerosis was shown to have an important role in internal cardiac autonomic dysfunction. Patients with left hippocampal sclerosis had more severe parasympathetic dysfunction as compared with those with right hippocampal sclerosis. In young individuals, mesial temporal sclerosis is commonly recognized with

temporal lobe epilepsy Temporal lobe epilepsy (TLE) is a chronic disorder of the nervous system which is characterized by recurrent, unprovoked focal seizures that originate in the temporal lobe of the brain and last about one or two minutes. TLE is the most common f ...

(TLE). On the other hand, it is an often unrecognized cause of cognitive decline, typically presenting with severe memory loss.

Temporal lobe epilepsy

Hippocampal sclerosis is often associated with

. Ammon's horn sclerosis (AHS) is the type of hippocampal sclerosis associated with mesial temporal lobe epilepsy. The terms are often used interchangeably but Ammon's horn sclerosis does not involve the

dentate gyrus The dentate gyrus (DG) is part of the hippocampal formation in the temporal lobe of the brain, which also includes the hippocampus and the subiculum. The dentate gyrus is part of the hippocampal trisynaptic circuit and is thought to contribute ...

. The type of neuronal loss in temporal lobe epilepsy (TLE), is primarily found in the hippocampus, and can be seen in approximately 65% of TLE cases. Sclerotic hippocampus is pointed to as the most likely origin of chronic seizures in temporal lobe epilepsy, rather than the

amygdala The amygdala (; plural: amygdalae or amygdalas; also '; Latin from Greek, , ', 'almond', 'tonsil') is one of two almond-shaped clusters of nuclei located deep and medially within the temporal lobes of the brain's cerebrum in complex verteb ...

or other

temporal lobe The temporal lobe is one of the four Lobes of the brain, major lobes of the cerebral cortex in the brain of mammals. The temporal lobe is located beneath the lateral fissure on both cerebral hemispheres of the mammalian brain. The temporal lobe ...

regions. Although hippocampal sclerosis has been identified as a distinctive feature of the pathology associated with temporal lobe epilepsy, this disorder is not merely a consequence of prolonged seizures as argued. A long and ongoing debate addresses the issue of whether hippocampal sclerosis is the cause or the consequence of chronic and pharmaceutically resistant seizure activity. Temporal

lobectomy Lobectomy means ''surgical excision of a lobe''. This may refer to a lobe of the lung (also simply called a lobectomy), a lobe of the thyroid (hemithyroidectomy), a lobe of the brain (as in anterior temporal lobectomy), or a lobe of the liver (h ...

is a common treatment for TLE, surgically removing the seizure focal area, though complications can be severe. Mesial temporal lobe epilepsy (MTLE), may be due to hippocampal sclerosis, or due to thalamic changes in temporal lobe epilepsy with and without hippocampal sclerosis,

Causes

Aging

Although hippocampal sclerosis is relatively commonly found among elderly people (≈10% of individuals over the age of 85 years), association between this disease and aging remains unknown.

Vascular risk factors

There were also observations that hippocampal sclerosis was associated with vascular risk factors. Hippocampal sclerosis cases were more likely than Alzheimer's disease to have had a history of

stroke A stroke is a medical condition in which poor blood flow to the brain causes cell death. There are two main types of stroke: ischemic, due to lack of blood flow, and hemorrhagic, due to bleeding. Both cause parts of the brain to stop functionin ...

(56% vs. 25%) or

hypertension Hypertension (HTN or HT), also known as high blood pressure (HBP), is a long-term medical condition in which the blood pressure in the arteries is persistently elevated. High blood pressure usually does not cause symptoms. Long-term high bl ...

(56% vs. 40%), evidence of small vessel disease (25% vs. 6%), but less likely to have had

diabetes mellitus Diabetes, also known as diabetes mellitus, is a group of metabolic disorders characterized by a high blood sugar level ( hyperglycemia) over a prolonged period of time. Symptoms often include frequent urination, increased thirst and increased ap ...

(0% vs. 22%).

Socioeconomic status

Socioeconomic correlates of health have been well established in the study of heart disease, lung cancer, and diabetes. Many of the explanations for the increased incidence of these conditions in people with lower

socioeconomic status Socioeconomic status (SES) is an economic and sociological combined total measure of a person's work experience and of an individual's or family's economic access to resources and social position in relation to others. When analyzing a family's ...

(SES) suggest they are the result of poor diet, low levels of exercise, dangerous jobs (exposure to toxins etc.) and increased levels of smoking and alcohol intake in socially deprived populations. Hesdorffer et al. found that low SES, indexed by poor education and lack of home ownership, was a risk factor for epilepsy in adults, but not in children in a population study. Low socioeconomic status may have a cumulative effect for the risk of developing epilepsy over a lifetime.

Diagnosis

Classification

Mesial temporal sclerosis is a specific pattern of

hippocampal The hippocampus (via Latin from Greek , 'seahorse') is a major component of the brain of humans and other vertebrates. Humans and other mammals have two hippocampi, one in each side of the brain. The hippocampus is part of the limbic system, an ...

neuron A neuron, neurone, or nerve cell is an electrically excitable cell that communicates with other cells via specialized connections called synapses. The neuron is the main component of nervous tissue in all animals except sponges and placozoa. N ...

cell loss.Bronen RA, Fulbright RK, Spencer DD, et al. 1997
Trepeta, Scott 2007 There are three specific patterns of cell loss. Cell loss might involve sectors CA1 and CA4, CA4 alone, or CA1 to CA4. Associated hippocampal

atrophy Atrophy is the partial or complete wasting away of a part of the body. Causes of atrophy include mutations (which can destroy the gene to build up the organ), poor nourishment, poor circulation, loss of hormonal support, loss of nerve supply t ...

and

is common. MRI scan commonly displays increased T2 signal and hippocampal atrophy. Mesial temporal sclerosis might occur with other temporal lobe abnormalities (dual pathology). Mesial temporal sclerosis is the most common pathological abnormality in

. It has been linked to abnormalities in

TDP-43 TAR DNA-binding protein 43 (TDP-43, transactive response DNA binding protein 43 kDa) is a protein that in humans is encoded by the ''TARDBP'' gene. Structure TDP-43 is 414 amino acid residues long. It consists of 4 domains: an N-terminal d ...

Treatment

It is refractory to treatment with anti-epileptics but surgically treatable with Hippocampectomy, sometimes amygdala is also removed.The procedure is known as Antero-medial temporal lobe resection.

References

External links

{{Limbic system Central nervous system disorders Epilepsy Disorders causing seizures Hippocampus (brain)