CADASIL may start with attacks of migraine with aura or subcortical transient ischemic attacks or strokes, or mood disorders between 35 and 55 years of age. The disease progresses to subcortical dementia associated with pseudobulbar palsy and urinary incontinence.

Ischemic strokes are the most frequent presentation of CADASIL, with approximately 85% of symptomatic individuals developing transient ischemic attacks or stroke(s). The mean age of onset of ischemic episodes is approximately 46 years (range 30–70). A classic lacunar syndrome occurs in at least two-thirds of affected patients while hemispheric strokes are much less common. It is worthy of note that ischemic strokes typically occur in the absence of traditional cardiovascular risk factors. Recurrent silent strokes, with or without clinical strokes, often lead to cognitive decline and overt subcortical dementia. A case of CADASIL presenting as schizophreniform organic psychosis has been reported.

Persons with HDLS can suffer from tremors, decreased body movement, unsteadiness (Parkinsonism, muscles on one side of the body in constant contraction (spastic hemiparesis), impairment in motor and sensory function in the lower extremities (paraparesis), paralysis resulting in partial or total loss of all extremities and torso (tetraparesis), and the lack of voluntary coordination of muscle movements (ataxia).

With symptoms of personality changes, behavioral changes, dementia, depression, and epilepsy, HDLS has been commonly misdiagnosed for a number of other diseases. Dementia or frontotemporal behavioral changes, for example, have commonly steered some clinicians to mistakenly consider diagnoses such as Alzheimer’s disease, frontotemporal dementia or atypical Parkinsonism. The presence of white matter changes has led to misdiagnosis of multiple sclerosis. HDLS commonly manifests with neuropsychiatric symptoms, progressing to dementia, and after a few years shows motor dysfunction. Eventually patients become wheelchair-bound or bedridden.

White matter degeneration is associated with and makes differential diagnoses out of other adult onset leukodystrophies such as metachromatic leukodystrophy (MLD), Krabbe disease (globoid cell leukodystrophy), and X-linked adrenoleukodystrophy (X-ADL).

CADASIL or CADASIL syndrome, involving cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy, is the most common form of hereditary stroke disorder, and is thought to be caused by mutations of the "Notch 3" gene on chromosome 19. The disease belongs to a family of disorders called the leukodystrophies. The most common clinical manifestations are migraine headaches and transient ischemic attacks or strokes, which usually occur between 40 and 50 years of age, although MRI is able to detect signs of the disease years prior to clinical manifestation of disease.

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.

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.

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.

The key symptom of RCVS is recurrent thunderclap headaches, which over 95% of patients experience. In two-thirds of cases, it is the only symptom. These headaches are typically bilateral, very severe and peak in intensity within a minute. They may last from minutes to days, and may be accompanied by nausea, photophobia, phonophobia or vomiting. Some patients experience only one headache, but on average there are four attacks over a period of one to four weeks. A milder, residual headache persists between severe attacks for half of patients.

1–17% of patients experience seizures. 8–43% of patients show neurologic problems, especially visual disturbances, but also hemiplegia, ataxia, dysarthria, aphasia, and numbness. These neurologic issues typically disappear within minutes or a few hours; more persistent symptoms may indicate a stroke. Posterior reversible encephalopathy syndrome is present in a small minority of patients.

This condition features the unique property that the patient's cerebral arteries can spontaneously constrict and relax back and forth over a period of time without intervention and without clinical findings. Vasospasm is common post subarachnoid hemorrhage and cerebral aneurysm, but in RCVS only 25% of patients have symptoms post subarachnoid hemorrhage.

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.

Onset usually occurs in childhood, however some adult cases have been found. Generally, physicians look for the symptoms in children. Symptoms include cerebellar ataxia, spasticity, optic atrophy, epilepsy, loss of motor functions, irritability, vomiting, coma, and even fever has been tied to VWM. The neurological disorders and symptoms which occur with VWM are not specific to countries; they are the same all over the world. Neurological abnormalities may not always be present in those who experience onset as adults. Symptoms generally appear in young children or infants who were previously developing fairly normally.

Most symptoms of people with post-viral cerebellar ataxia deal to a large extent with the movement of the body. Some common symptoms that are seen are clumsy body movements and eye movements, difficulty walking, nausea, vomiting, and headaches.

Reversible cerebral vasoconstriction syndrome (RCVS, sometimes called Call-Fleming syndrome) is a disease characterized by a weeks-long course of thunderclap headaches, sometimes focal neurologic signs, and occasionally seizures. Symptoms are thought to arise from transient abnormalities in the blood vessels of the brain. In some cases, it may be associated with childbirth, vasoactive or illicit drug use, or complications of pregnancy.

For the vast majority of patients, all symptoms disappear on their own within three weeks. Deficits persist in a small minority of patients, with severe complications or death being very rare. Because symptoms resemble a variety of life-threatening conditions, differential diagnosis is necessary.

Differential diagnosis may include:

- Opsoclonus-myoclonus-ataxia syndrome

- Miller-Fisher syndrome

- Meningoencephalitis

- Cerebral abscess

- Tumor

- Hydrocephalus

- Inner-ear Disease

- Acute Vestibulitis

- Acute Labyrinthitis

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.

Diffuse myelinoclastic sclerosis, sometimes referred to as Schilder's disease, is a very infrequent neurodegenerative disease that presents clinically as pseudotumoural demyelinating lesions, that make its diagnosis difficult. It usually begins in childhood, affecting children between 5 and 14 years old, but cases in adults are possible.

This disease is considered one of the borderline forms of multiple sclerosis because some authors consider them different diseases and others MS variants. Other diseases in this group are neuromyelitis optica (NMO), Balo concentric sclerosis and Marburg multiple sclerosis.

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.

The diagnosis of PMG is merely descriptive and is not a disease in itself, nor does it describe the underlying cause of the brain malformation.

Polymicrogyria may be just one piece of a syndrome of developmental abnormalities, because children born with it may suffer from a wide spectrum of other problems, including global developmental disabilities, mild to severe mental retardation, motor dysfunctions including speech and swallowing problems, respiratory problems, and seizures. Though it is difficult to make a predictable prognosis for children with the diagnosis of PMG, there are some generalized clinical findings according to the areas of the brain that are affected.

- Bilateral frontal polymicrogyria (BFP) – Cognitive and motor delay, spastic quadriparesis, epilepsy

- Bilateral frontoparietal polymicrogyria (BFPP) – Severe cognitive and motor delay, seizures, dysconjugate gaze, cerebellar dysfunction

- Bilateral perisylvian polymicrogyria (BPP) – Pseudobulbar signs, cognitive impairment, epilepsy, some with arthrogryposis or lower motor neuron disease

- Bilateral parasagittal parieto-occipital polymicrogyria (BPPP) – Partial seizures, some with mental retardation

- Bilateral generalized polymicrogyria (BGP) – Cognitive and motor delay of variable severity, seizures

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.

BGP is most severe in the perisylvian regions, but occurs in a generalised distribution. Associated factors include a reduced volume of white matter and ventriculomegaly. BGP tends to show excessively folded and fused gyri of an abnormally thin cerebral cortex, and an absence of the normal six-layered structure. The abnormally thin cortex is a key factor that distinguishes this form of polymicrogyria from the others, which are characterized by an abnormally thick cortex. Most of the patients have cognitive and motor delay, spastic hemi- or quadriparesis, and seizures in varying degrees. The seizures also vary at age of onset, type, and severity. There have been pseudobulbar signs reported with BGP, which are also seen in patients suffering from BPP. This association leads to the belief that there is overlap between patients suffering from BGP and patients suffering from grade 1 BPP.

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.

Often with VWM, the lack of knowledge of the disease causes a misdiagnosis among physicians. As VWM is a member of the large group of leukodystrophy syndromes, it is often misdiagnosed as another type such as metachromatic leukodystrophy. More often than not, it is simply classified as a non-specific leukodystrophy. The characteristics of the brain upon autopsy are often very similar to atypical diffuse sclerosis, such as the presence of fibrillary astrocytes and scant sudanophilic lipids. Adult-onset VWM disease can present with psychosis and may be hard to differentiate from schizophrenia. Common misdiagnosis from misinterpreting the MRI include asphyxia, congential infections, metabolic diseases.

Multiple Sclerosis is often a misdiagnosis, but only in children due to its neurological characteristics, onset in early years, and MRI abnormalities. However, there are many differences between the two diseases. The glial cells express a loss of myelin. This loss of myelin is different from that seen in other diseases where hypomyelination occurs. In VWM, the cells never produce the normal amounts, whereas with diseases like MS, the cells' normal amounts are deteriorated. Also, with MS, the demyelination occurs due to inflammation, which is not the case in VWM. Cell differences include a lower penetration of the macrophages and microglia, as well as the lack of T cells and B cells in VWM. Finally, patients with MS have widespread demyelination, but those with VWM only express demyelination in a localized area.

Approximately 2 million people in the world suffer from multiple sclerosis Tumefactive multiple sclerosis cases make up 1 to 2 of every 1000 multiple sclerosis cases. This means that only around 2000 people in the world suffer of tumefactive MS. Of those cases, there is a higher percentage of females affected than males. The median age of onset is 37 years.

As in general MS, there are differences for gender, ethnicity and geographic location. Based on epidemiological studies, there are about 3 times more female MS patients than male patients, indicating a possibility of an increased risk due to hormones. Among different ethnic groups, MS is the most common among Caucasians and seems to have a greater incidence at latitudes above 40° as compared to at the equator. While these associations have been made, it is still unclear how they result in an increased risk of MS onset.

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.

Some NMO patients present double positive for autoantibodies to AQP4 and MOG. These patients have MS-like brain lesions, multifocal spine lesions and retinal and optic nerves atrophy.

Transneuronal degeneration can be grouped into two general categories: anterograde and retrograde.