Ammon's horn (or hippocampal) sclerosis (AHS) is the most common type of neuropathological damage seen in individuals with temporal lobe epilepsy. This type of neuron cell loss, primarily in the hippocampus, can be observed in approximately 65% of people suffering from this form of epilepsy. Sclerotic hippocampus is pointed to as the most likely origin of chronic seizures in temporal lobe epilepsy patients, rather than the amygdala or other 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 is a common treatment for TLE, surgically removing the seizure focal area, though complications can be severe.

Other variants of temporal lobe epilepsy include mesial temporal lobe epilepsy (MTLE), MTLE due to hippocampal sclerosis, thalamic changes in temporal lobe epilepsy with and without hippocampal sclerosis, and hippocampal sclerosis with and without mesial temporal lobe epilepsy.

Hippocampal sclerosis (HS) is a neuropathological condition with severe neuronal cell loss and gliosis in the hippocampus, specifically in the CA-1 (Cornu Ammonis area 1) and subiculum of the hippocampus. It was first described in 1880 by Wilhelm Sommer. Hippocampal sclerosis is a frequent pathologic finding in community-based dementia. Hippocampal sclerosis can be detected with autopsy or MRI. Individuals with hippocampal sclerosis have similar initial symptoms and rates of dementia progression to those with Alzheimer's disease (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 and social impact related to epilepsy, as well as side effects associated with antiepileptic treatments.

Other medical conditions with similar symptoms include panic attacks, psychosis spectrum disorders, tardive dyskinesia, and occipital lobe epilepsy.

The diagnosis of temporal lobe epilepsy can include the following methods: Magnetic resonance imaging (MRI), CT scans, positron emission tomography (PET), EEG, and magnetoencephalography.

A focal impaired awareness seizure is a seizure that is associated with unilateral cerebral hemisphere involvement and causes impairment of awareness or responsiveness, i.e. alteration of consciousness.

- Presentation

Focal impaired awareness seizures are often preceded by an aura. The seizure aura is a focal aware seizure. The aura may manifest itself as a feeling of déjà vu, jamais vu, fear, euphoria or depersonalization. The aura might also occur as a visual disturbance, such as tunnel vision or a change in the perceived size of objects. Once consciousness is impaired, the person may display automatisms such as lip smacking, chewing or swallowing. There may also be loss of memory (amnesia) surrounding the seizural event. The person may still be able to perform routine tasks such as walking, although such movements are not purposeful or planned. Witnesses may not recognize that anything is wrong.

Focal impaired awareness seizures might arise from any lobe of the brain. They most commonly arise from the temporal lobe, particularly the amygdala, hippocampus, and neocortical regions. A common associated brain abnormality is mesial temporal sclerosis. Mesial temporal sclerosis is a specific pattern of hippocampal neuronal loss accompanied by hippocampal gliosis and atrophy. Focal onset impaired awareness seizures occur when excessive and synchronous electrical brain activity causes the impaired awareness and responsiveness. The abnormal electrical activity might spread to the rest of the brain and cause a "focal to bilateral seizure" or a generalized tonic–clonic seizure. The newer classification of 2017 groups only focal and generalized seizures, and generalised seizures are those that involve both sides of the brain from the onset.

Movement Disorder

- Dystonia

- Parkinsonism

- Chorea

- Ocular flutter

- Motor tics

Psychiatric Symptoms

- Agitation

- Emotional lability

- Psychosis

- Depression

Associated symptoms

- Encephalopathy

- Sleep disorder

- Reduced consciousness

- Mutism

Based on syndrome with focal or diffuse neurological dysfunction associated with fever. Inflammatory lesion in MRI and CSF pleocytosis. EEG signs of encephalitis.

Focal aware seizures are seizures which affect only a small region of the brain, often the temporal lobes or structures found there such as the hippocampi. People who have focal aware seizures remain conscious. Focal aware seizures often precede larger focal impaired awareness seizures, where the abnormal electrical activity spreads to a larger area of the brain. This can result in a tonic-clonic seizure.

- Presentation

Focal onset aware seizures are a very subjective experience, and the symptoms vary greatly between people. This is due to the varying locations of the brain the seizures originate in e.g.: Rolandic. A focal aware seizure may go unnoticed by others or shrugged off by the sufferer as merely a "funny turn." Focal aware seizures usually start suddenly and are very brief, typically lasting 60 to 120 seconds.

Some common symptoms of a focal onset aware seizure, when the person is awake, are:

- preserved consciousness

- sudden and inexplicable feelings of fear, anger, sadness, happiness or nausea

- sensations of falling or movement

- experiencing of unusual feelings or sensations

- altered sense of hearing, smelling, tasting, seeing, and tactile perception (sensory illusions or hallucinations), or feeling as though the environment is not real (derealization) or dissociation from the environment or self (depersonalization)

- a sense of spatial distortion—things close by may appear to be at a distance

- déjà vu (familiarity) or jamais vu (unfamiliarity)

- laboured speech or inability to speak at all

- usually the event is remembered in detail

When the seizure occurs during sleep, the person will often become semi-conscious and act out a dream they were having while engaging with the real environment as normal. Objects and people usually appear normal or only slightly distorted to them, and will be able to communicate with them on an otherwise normal level.

However, since the person is still acting in the dream-like state from which they woke, they will assimilate any hallucinations or delusions into their communication, often speaking to a hallucinatory person or speaking of events or thoughts normally pertaining to the dream they were having or other hallucination.

While asleep symptoms include:

- onset usually in REM sleep

- dream like state

- appearance of full consciousness

- hallucinations or delusions

- behavior or visions typical in dreams

- ability to engage with the environment and other people as in full consciousness, though often behaving abnormally, erratically, or failing to be coherent

- complete amnesia or assimilating the memory as though it was a normal dream on regaining full consciousness

Although hallucinations may occur during focal aware seizures they are differentiated from psychotic symptoms by the fact that the person is usually aware that the hallucinations are not real.

- Jacksonian march

Jacksonian march or Jacksonian seizure is a phenomenon where a focal aware seizure spreads from the distal part of the limb toward the face (on same side of body). They involve a progression of the location of the seizure in the brain, which leads to a "march" of the motor presentation of symptoms.

Jacksonian seizures are initiated with abnormal electrical activity within the primary motor cortex. They are unique in that they travel through the primary motor cortex in succession, affecting the corresponding muscles, often beginning with the fingers. This is felt as a tingling sensation, or a feeling of waves through the fingers when touched together. It then affects the hand and moves on to more proximal areas on the same side of body. Symptoms often associated with a Jacksonian seizure are sudden head and eye movements, tingling, numbness, smacking of the lips, and sudden muscle contractions. Most of the time any one of these actions can be seen as normal movements, without being associated with the seizure occurring. They occur at no particular moment and last only briefly. They may result in secondary generalized seizure involving both hemispheres. They can also start at the feet, manifesting as tingling or pins and needles, and there are painful cramps in the foot muscles, due to the signals from the brain. Because it is a partial seizure, the postictal state is of normal consciousness .

Symptoms of standard MS consist of both sensory and motor symptoms. The more common symptoms include spasticity, visual loss, difficulty in walking and paresthesia which is a feeling of tickling or numbness of the skin. but symptoms of tumefactive MS are not so clear. They often mimic a variety of other diseases including ischemic stroke, peroneal nerve palsy and intracranial neurologic disease.

Subjects have been reported to suffer from a decreased motor control resulting in a ‘foot drop’, or significantly reduced leg movement. In other cases closer mimicking strokes, subjects may suffer from confusion, dizziness, and weakness in one side of the face. Symptoms also can mimic a neoplasm with symptoms such as headaches, aphasia, and/ or seizures.[13]

There are some differences with normal MS symptoms.

Spasticity is not as in tumefactive cases, because it standard MS it is caused by demyelination or inflammation in the motor areas of the brain or the spinal cord. This upper motor neuron syndrome appears when motor control of skeletal muscles is affected due to damage to the efferent motor pathways. Spasticity is an involuntary muscle movement like an exaggerated stretch reflex, which is when a muscle overcompensates and contracts too much in response to the muscle being stretched. It is believed that spasticity is the result of the lack of inhibitory control on the muscles, an effect of neuronal damage.

Visual loss or disturbances are also different. In standard MS are a result of inflammation of the optic nerve, known as optic neuritis. The effects of optic neuritis can be loss of color perception and worsening vision. Vision loss usually starts off centrally in one eye and may lead to complete loss of vision after a period of time.

The possible cognitive dysfunction is also rare in tumefactive cases. MS patients may show signs of cognitive impairment where there is a reduction in the speed of information processing, a weaker short-term memory and a difficulty in learning new concepts. This cognitive impairment is associated with the loss of brain tissue, known as brain atrophy which is a result of the demyelination process in MS.

About fatigue, most MS patients experience fatigue and this could be a direct result of the disease, depression or sleep disturbances due to MS. It is not clearly understood how MS results in physical fatigue but it is known that the repetitive usage of the same neural pathways results in nerve fiber fatigue that could cause neurological symptoms. Such repeated usage of neural pathways include continuous reading which may result in temporary vision failure.

Symptoms are similar to those in multiple sclerosis and may include dementia, aphasia, seizures, personality changes, poor attention, tremors, balance instability, incontinence, muscle weakness, headache, vomiting, and vision and speech impairment.

Agnosia is the inability to recognize certain objects, persons or sounds. Agnosia is typically caused by damage to the brain (most commonly in the occipital or parietal lobes) or from a neurological disorder. Treatments vary depending on the location and cause of the damage. Recovery is possible depending on the severity of the disorder and the severity of the damage to the brain. Many more specific types of agnosia diagnoses exist, including: associative visual agnosia, astereognosis, auditory agnosia, auditory verbal agnosia, prosopagnosia, simultanagnosia, topographical disorientation, visual agnosia etc.

Memory disorders are the result of damage to neuroanatomical structures that hinders the storage, retention and recollection of memories. Memory disorders can be progressive, including Alzheimer's disease, or they can be immediate including disorders resulting from head injury.

A person with MS can have almost any neurological symptom or sign, with autonomic, visual, motor, and sensory problems being the most common. The specific symptoms are determined by the locations of the lesions within the nervous system, and may include loss of sensitivity or changes in sensation such as tingling, pins and needles or numbness, muscle weakness, blurred vision, very pronounced reflexes, muscle spasms, or difficulty in moving; difficulties with coordination and balance (ataxia); problems with speech or swallowing, visual problems (nystagmus, optic neuritis or double vision), feeling tired, acute or chronic pain, and bladder and bowel difficulties, among others. Difficulties thinking and emotional problems such as depression or unstable mood are also common. Uhthoff's phenomenon, a worsening of symptoms due to exposure to higher than usual temperatures, and Lhermitte's sign, an electrical sensation that runs down the back when bending the neck, are particularly characteristic of MS. The main measure of disability and severity is the expanded disability status scale (EDSS), with other measures such as the multiple sclerosis functional composite being increasingly used in research.

The condition begins in 85% of cases as a clinically isolated syndrome (CIS) over a number of days with 45% having motor or sensory problems, 20% having optic neuritis, and 10% having symptoms related to brainstem dysfunction, while the remaining 25% have more than one of the previous difficulties. The course of symptoms occurs in two main patterns initially: either as episodes of sudden worsening that last a few days to months (called relapses, exacerbations, bouts, attacks, or flare-ups) followed by improvement (85% of cases) or as a gradual worsening over time without periods of recovery (10–15% of cases). A combination of these two patterns may also occur or people may start in a relapsing and remitting course that then becomes progressive later on. Relapses are usually not predictable, occurring without warning. Exacerbations rarely occur more frequently than twice per year. Some relapses, however, are preceded by common triggers and they occur more frequently during spring and summer. Similarly, viral infections such as the common cold, influenza, or gastroenteritis increase their risk. Stress may also trigger an attack. Women with MS who become pregnant experience fewer relapses; however, during the first months after delivery the risk increases. Overall, pregnancy does not seem to influence long-term disability. Many events have been found not to affect relapse rates including vaccination, breast feeding, physical trauma, and Uhthoff's phenomenon.

Several phenotypes (commonly termed "types"), or patterns of progression, have been described. Phenotypes use the past course of the disease in an attempt to predict the future course. They are important not only for prognosis but also for treatment decisions. Currently, the United States National Multiple Sclerosis Society and the Multiple Sclerosis International Federation, describes four types of MS (revised in 2013):

1. Clinically isolated syndrome (CIS)

2. Relapsing-remitting MS (RRMS)

3. Primary progressive MS (PPMS)

4. Secondary progressive MS (SPMS)

Relapsing-remitting MS is characterized by unpredictable relapses followed by periods of months to years of relative quiet (remission) with no new signs of disease activity. Deficits that occur during attacks may either resolve or leave problems, the latter in about 40% of attacks and being more common the longer a person has had the disease. This describes the initial course of 80% of individuals with MS. When deficits always resolve between attacks, this is sometimes referred to as "benign MS", although people will still build up some degree of disability in the long term. On the other hand, the term "malignant multiple sclerosis" is used to describe people with MS having reached significant level of disability in a short period. The relapsing-remitting subtype usually begins with a clinically isolated syndrome (CIS). In CIS, a person has an attack suggestive of demyelination, but does not fulfill the criteria for multiple sclerosis. 30 to 70% of persons experiencing CIS later develop MS.

Primary progressive MS occurs in approximately 10–20% of individuals, with no remission after the initial symptoms. It is characterized by progression of disability from onset, with no, or only occasional and minor, remissions and improvements. The usual age of onset for the primary progressive subtype is later than of the relapsing-remitting subtype. It is similar to the age that secondary progressive usually begins in relapsing-remitting MS, around 40 years of age.

Secondary progressive MS occurs in around 65% of those with initial relapsing-remitting MS, who eventually have progressive neurologic decline between acute attacks without any definite periods of remission. Occasional relapses and minor remissions may appear. The most common length of time between disease onset and conversion from relapsing-remitting to secondary progressive MS is 19 years.

Other, unusual types of MS have been described; these include Devic's disease, Balo concentric sclerosis, Schilder's diffuse sclerosis, and Marburg multiple sclerosis. There is debate on whether they are MS variants or different diseases. Multiple sclerosis behaves differently in children, taking more time to reach the progressive stage. Nevertheless, they still reach it at a lower average age than adults usually do.

Cognitive symptoms from steroids appear within the first few weeks of treatment, appear to be dose dependent, and may or may not be accompanied by steroid psychosis or other Cushing's-type symptoms.

The symptoms include deficits in

- verbal and non-verbal memory

- working memory

- attention

- sustained concentration

- executive function

- psychomotor speed

- academic or occupational performance.

These symptoms have been shown to improve within months to a year after discontinuing glucocorticoid medication, but residual impairments following prolonged steroid use can remain.

Tumefactive multiple sclerosis is a condition in which the central nervous system of a person has multiple demyelinating lesions with atypical characteristics for those of standard multiple sclerosis (MS). It is called tumefactive as the lesions are "tumor-like" and they mimic tumors clinically, radiologically and sometimes pathologically.

These atypical lesion characteristics include a large intracranial lesion of size greater than 2.0 cm with a mass effect, edema and an open ring enhancement. A mass effect is the effect of a mass on its surroundings, for example, exerting pressure on the surrounding brain matter. Edema is the build-up of fluid within the brain tissue. Usually, the ring enhancement is directed toward the cortical surface. The tumefactive lesion may mimic a malignant glioma or cerebral abscess causing complications during the diagnosis of tumefactive MS. T2-hypointense rim and incomplete ring enhancement of the lesions on post-gadolinium T1- weighted imaging on brain MRI enable accurate diagnosis of TDL

Normally a tumefactive demyelinating lesion appears together with smaller disseminated lesions separated in time and space, yielding a diagnosis of Multiple Sclerosis. Hence the name "tumefactive multiple sclerosis". When the demyelinating lesion appears alone it has been termed solitary sclerosis. These cases belong to a multiple sclerosis borderline and there is not a universal agreement about how should them be considered.

Tumefactive multiple sclerosis is a demyelinating and inflammatory disease. Myelination of the axons are highly important for signalling as this improves the speed of conduction of action potentials from one axon to the next. This is done through the formation of high-resistance, low-conductance myelin sheaths around the axons by specific cells called oligodendrocytes. As such, the demyelination process affects the communication between neurons and this consequently affects the neural pathways they control. Depending on where the demyelination takes place and its severity, patients with tumefactive MS have different clinical symptoms.

The typical demyelinating plaques in Schilder's sclerosis are usually found bilaterally in the semioval center; both hemispheres are almost completely occupied by large, well defined lesions. Although plaques of this kind are largely prevalent in Schilder's sclerosis, smaller lesions can also be observed.

Ocular dysmetria is a form of dysmetria that involves the constant under- or over-shooting of the eyes when attempting to focus gaze on something.

Ocular dysmetria indicates lesions in the cerebellum, which is the brain region responsible for coordinating movement. It is a symptom of several neurological conditions including multiple sclerosis.

It is a condition that can cause symptoms similar to sea sickness.

Source of information: Mult-sclerosis.org

Inflammatory demyelinating diseases (IDDs), sometimes called Idiopathic (IIDDs) because the unknown etiology of some of them, and sometimes known as borderline forms of multiple sclerosis, is a collection of multiple sclerosis variants, sometimes considered different diseases, but considered by others to form a spectrum differing only in terms of chronicity, severity, and clinical course.

Multiple Sclerosis for some people is a syndrome more than a single disease. It can be considered among the acquired demyelinating syndromes with a multiphasic instead of monophasic behaviour. Multiple sclerosis also has a prodromal stage in which an unknown underlying condition, able to damage the brain, is present, but no lesion has still developed.

In a recent analysis (Susac et al., 2003), MRI images from 27 patients fulfilling the diagnostic criteria of Susac's syndrome were reviewed. Multifocal supratentorial lesions were present in all patients. Most lesions were small (3 to 7 mm), though some were larger than 7 mm. All 27 patients had corpus callosum lesions. These all had a punched-out appearance on follow up MRI. Though most commonly involving white matter, many patients also had lesions in deep grey matter structures, as well as leptomeningeal enhancement. Multiple sclerosis (MS) and acute disseminated encephalomyelitis (ADEM) can mimic the MRI changes seen in patients with Susac's syndrome. However, the callosal lesions in Susac's syndrome are centrally located. In comparison, patients with MS and ADEM typically have lesions involving the undersurface of the corpus callosum. Deep gray matter involvement commonly occurs in ADEM but is very rare in MS. Leptomeningeal involvement is not typical of either MS or ADEM. What this means is that if 10 lesions are found in the brain of an MS patient, a lesion may be found in the corpus callosum. If you have 10 lesions in a Susac patient, more than half will be in the corpus callosum.

A concern about this illness is that it mimics multiple sclerosis when looking at the vision loss and brain lesions. If close attention is not paid to the retina of a patient with vision loss and brain lesions, their symptoms may be mistaken for MS instead of Susac's syndrome. This may account for the low prevalence of the illness. There is also a pathological similarity between the endotheliopathy in Susac's syndrome with that seen in juvenile dermatomyositis.

Symptoms can develop over several weeks to months. Symptoms depend on location of damage in the brain and the degree of damage. The most prominent symptoms are "clumsiness, progressive weakness and visual, speech, and sometimes personality changes"

The lesions affecting the parietal and occipital lobes can lead to a phenomenon known as alien hand syndrome.

Symptoms of JPLS begin in early childhood and progress over a period of 15 to 20 years. Early symptoms include clumsiness, muscle spasms, weakness and stiffness in the legs, and difficulty with balance. As symptoms progress, they become more serious and include weakness and stiffness in the arms and hands, slurred speech, drooling, difficulty swallowing, and an inability to walk.

Patients typically present with low frequency hearing loss detectable via an audiogram. Headaches are frequently present in addition to roaring tinnitus and often some degree of paranoia. Partial vision loss is often present and caused by branch retinal artery occlusions. The presence of refractile or non-refractile yellow Gass plaques in the retinal arterioles is near pathognomonic for the disease. Fluorescein angiography may demonstrate leakage in areas remote from the retinal infarctions.

Balo concentric sclerosis is a disease in which the white matter of the brain appears damaged in concentric layers, leaving the axis cylinder intact. It was described by Joszef Balo who initially named it "leuko-encephalitis periaxialis concentrica" from the previous definition, and it is currently considered one of the borderline forms of multiple sclerosis.

Balo concentric sclerosis is a demyelinating disease similar to standard multiple sclerosis, but with the particularity that the demyelinated tissues form concentric layers. Scientists used to believe that the prognosis was similar to Marburg multiple sclerosis, but now they know that patients can survive, or even have spontaneous remission and asymptomatic cases.

It is also common that the clinical course is primary progressive, but a relapsing-remitting course has been reported.

It seems that the course gets better with prednisone therapy, although evidence of this is anecdotal and such conclusions are difficult to accept given that there are cases where patients spontaneously recover whether the patient was on steroid therapy or not.

Steroid dementia syndrome describes the signs and symptoms of hippocampal and prefrontal cortical dysfunction, such as deficits in memory, attention, and executive function, induced by glucocorticoids. Dementia-like symptoms have been found in some individuals who have been exposed to glucocorticoid medication, often dispensed in the form of asthma, arthritis, and anti-inflammatory steroid medications. The condition reverses, but not always completely, within months after steroid treatment is stopped.

The term "steroid dementia" was coined by Varney et al. (1984) in reference to the effects of long-term glucocorticoid use in 1,500 patients. While the condition generally falls under the classification of Cushing's syndrome, the term "steroid dementia syndrome" is particularly useful because it recognizes both the cause of the syndrome and the specific effects of glucocorticoids on cognitive function. Further, the more precise terminology clearly distinguishes the condition from full-blown Cushing's syndrome, which is extremely broad regarding the causes (endogenous or exogenous, pituitary or adrenal) and the multitude of symptoms (ranging from skin disorders to osteoporosis), and from hypercortisolemia, which identifies neither the source nor the symptoms of excess circulatory cortisol.