Diabetic neuropathy affects all peripheral nerves including sensory neurons, motor neurons, but rarely affects the autonomic nervous system. Therefore, diabetic neuropathy can affect all organs and systems, as all are innervated. There are several distinct syndromes based on the organ systems and members affected, but these are by no means exclusive. A patient can have sensorimotor and autonomic neuropathy or any other combination. Signs and symptoms vary depending on the nerve(s) affected and may include symptoms other than those listed. Symptoms usually develop gradually over years.

Symptoms may include the following:

- Trouble with balance

- Numbness and tingling of extremities

- Dysesthesia (abnormal sensation to a body part)

- Diarrhea

- Erectile dysfunction

- Urinary incontinence (loss of bladder control)

- Facial, mouth and eyelid drooping

- Vision changes

- Dizziness

- Muscle weakness

- Difficulty swallowing

- Speech impairment

- Fasciculation (muscle contractions)

- Anorgasmia

- Retrograde ejaculation (in males)

- Burning or electric pain

Beyond early-onset and treatment-resistant cluster seizures, PCDH19 gene-related epilepsy is usually, but not always, associated with cognitive and sensory impairment of varying degrees, and psychiatric and behavioral problems. It is estimated that up to 60 to 75% of the females have cognitive deficits, ranging from mild to severe intellectual disability, which do not appear to be related to frequency or severity of seizures. Development over the course of a female patients’ childhood can follow one of three courses: delays from birth that persist into adulthood, normal development and then regression, or normal intellectual development. It is not yet clear why some people experience delayed intellectual growth and others regress with epilepsy.

From the University of Melbourne study, two-thirds of PCDH19 gene-related epilepsy patients have borderline intellectual functioning or intellectual disability, while one third have normal intelligence. A connection to depression, autism, obsessive and aggressive behaviors and other disorders has been observed in PCDH19 gene-related epilepsy. Approximately 40-60% of girls diagnosed with a PCDH19 mutation are on the autism spectrum.

Many of those with PCDH19 gene mutations also exhibit behavioral and psychological problems – including ADHD, aggression, obsessive-compulsive disorder, and anxiety. Other neurological abnormalities may present, including sleep disturbances, ictal apnea, motor deficits, hypotonia, language delay, sensory integration problems and dysautonomia.

The hallmark characteristic of PCDH19 gene-related epilepsy is early-onset cluster seizures that often cause cyanotic spells, which start in infancy or early childhood. The onset of the first cluster of seizures usually coincides with a fever (febrile seizures), however subsequent seizures may be febrile or afebrile. The seizure clusters are generally brief seizures, lasting 1–5 minutes, often accompanied by fearful screaming observed in 63% of girls. These cluster seizures can occur more than 10 times a day over several days, with varying amounts of time between seizure clusters.

Over time, children with PCDH19 gene-related epilepsy tend to exhibit multiple seizure types, including focal, generalized tonic-clonic, tonic, atonic, myclonus, and absence seizures. In a small study of 35 female patients with PCDH19 gene-related epilepsy, rare episodes of status epilepticus occurred in about 30% of patients in the early course of the disorder.

In PCDH19 gene-related epilepsy, the seizures are often refractory to treatment, especially in infancy and childhood. Additionally, seizures are usually characterized by persistence of cluster seizures, with variable frequency. In a study of 35 female patients with PCDH19 gene-related epilepsy, approximately 30% had become seizure free in the girl's childhood (mean age of 12 years), yet some continued into adulthood. In the same study, a few patients still had recurrent cluster seizures that evolved into status epilepticus in childhood or early adolescence.

Diabetic neuropathies are nerve damaging disorders associated with diabetes mellitus. These conditions are thought to result from a diabetic microvascular injury involving small blood vessels that supply nerves (vasa nervorum) in addition to macrovascular conditions that can accumulate in diabetic neuropathy. Relatively common conditions which may be associated with diabetic neuropathy include third, fourth, or sixth cranial nerve palsy; mononeuropathy; mononeuropathy multiplex; diabetic amyotrophy; a painful polyneuropathy; autonomic neuropathy; and thoracoabdominal neuropathy.

Drug-resistant epilepsy (DRE), also known as refractory epilepsy or pharmacoresistant epilepsy, is defined as failure of adequate trials of two tolerated and appropriately chosen and used antiepileptic drugs (AED schedules) (whether as monotherapies or in combination) to achieve sustained seizure freedom. The probability that the next medication will achieve seizure freedom drops with every failed AED; for example after two failed AEDs the probability that the third will achieve seizure freedom is around 4%. Drug-resistant epilepsy is commonly diagnosed after several years of uncontrolled seizures however in most cases it is evident much earlier. Approximately 30% of people with epilepsy have a drug-resistant form.

When 2 AEDs regimens have failed to produce sustained seizure-freedom, it is important to initiate other treatments to control seizures. Next to indirect consequences like injuries from falls, accidents, drowning and impairment in daily life, seizure control is critical because uncontrolled seizures -specifically generalized tonic clonic seizures- can damage the brain and increase the risk for sudden unexpected death in epilepsy called SUDEP. The first step is for physicians to refer their DRE patients to an epilepsy center in which a presurgical evaluation can be carried out in order to assess whether a patient is a candidate for epilepsy surgery or not. For those patients who are not surgical candidates, those who decline brain surgery or those in which brain surgery fails to produce long term seizure freedom, vagus nerve stimulation and/or a diet can be recommended.

The most common symptoms of acquired and transient cortical blindness include:

- A complete loss of visual sensation and of vision

- Preservation/sparing of the abilities to perceive light and/or moving, but not static objects (Riddoch syndrome)

- A lack of visual fixation and tracking

- Denial of visual loss (Anton–Babinski syndrome)

- Visual hallucinations

- Macular sparing, in which vision in the fovea is spared from the blindness.

Cortical blindness is the total or partial loss of vision in a normal-appearing eye caused by damage to the brain's occipital cortex. Cortical blindness can be acquired or congenital, and may also be transient in certain instances. Acquired cortical blindness is most often caused by loss of blood flow to the occipital cortex from either unilateral or bilateral posterior cerebral artery blockage (ischemic stroke) and by cardiac surgery. In most cases, the complete loss of vision is not permanent and the patient may recover some of their vision (Cortical visual impairment). Congenital cortical blindness is most often caused by perinatal ischemic stroke, encephalitis, and meningitis.

Rarely, a patient with acquired cortical blindness may have little or no insight that they have lost vision, a phenomenon known as Anton–Babinski syndrome.

Cortical blindness and cortical visual impairment (CVI), which refers to the partial loss of vision caused by cortical damage, are both classified as subsets of neurological visual impairment (NVI). NVI and its three subtypes—cortical blindness, cortical visual impairment, and delayed visual maturation—must be distinguished from ocular visual impairment in terms of their different causes and structural foci, the brain and the eye respectively. One diagnostic marker of this distinction is that the pupils of individuals with cortical blindness will respond to light whereas those of individuals with ocular visual impairment will not.

In 82% of epilepsy patients the heart rate increases quickly and suddenly upon a seizure This is known as ictal tachycardia. Ictal tachycardia is so characteristic that it can be distinguished from the slow gradual increase of heart rate that occurs during physical activity. This way in the majority of epilepsy patients seizures can be detected in the ECG. In addition to classical VNS, some new VNS generators continuously monitor heart rate and identify fast and sudden heart rate increases associated with seizures with intelligent software. Then an automatic additional stimulation can be triggered to interrupt, prevent or alleviate the seizure. This new generator type was shown to detect and treat at least four out of five seizures and 60% of seizures were shown to be interrupted with this heart-rate triggered stimulation. The earlier in the course of the seizure the stimulation occurred the quicker the seizure ended generally seizures were shown to be reduced by around 35% by stimulation