What are the other Names for this Condition? (Also known as/Synonyms)

• Neuronal Intranuclear Hyaline Inclusion Disease
• NIID (Neuronal Intranuclear Inclusion Disease)

What is Neuronal Intranuclear Inclusion Disease? (Definition/Background Information)

• Neuronal Intranuclear Inclusion Disease (NIID) is a slowly progressive, neurodegenerative disease. NIID may affect any part of the nervous system (central, peripheral, and/or autonomic), as well as various organs. Signs and symptoms may begin anywhere from infancy to late adulthood, and can vary from person to person. In most cases, the disease begins in childhood
• Symptoms of NIID worsen over time and may include dementia, limb weakness, cerebellar ataxia, dystonia, parkinsonism, seizures, and autonomic dysfunction. Therefore, people with NIID may have impairment of balance, movement, cognition, communication, behavior, and the ability to function independently. In general, limb weakness and ataxia are more common in children with NIID, while dementia is more common in people diagnosed in adulthood
• The features of Neuronal Intranuclear Inclusion Disease result from the presence of eosinophilic intranuclear inclusions inside neurons and glial cells (abnormal masses of substances in the nuclei of cells of the nervous system). The reason this occurs is not known. Both sporadic and familial cases have been reported. However, specific genes known to cause NIID have not yet been found
• Currently there is no treatment that cures or slows the progression of Neuronal Intranuclear Inclusion Disease, but medications that help control symptoms may improve quality of life. While the disease is ultimately fatal, life expectancy can range significantly, from one year to several decades after the diagnosis

(Source: Neuronal Intranuclear Inclusion Disease; Genetic and Rare Diseases Information Center (GARD) of National Center for Advancing Translational Sciences (NCATS), USA.)

Who gets Neuronal Intranuclear Inclusion Disease? (Age and Sex Distribution)

• Neuronal Intranuclear Inclusion Disease is a very rare disorder, with about 30 cases reported in the medical literature
• The onset of disease symptoms may occur in infancy, adolescence or adulthood, although in most cases, the manifestation begins in childhood
• Both genders may be affected by this disorder
• Worldwide, all ethnicities and populations may be affected

What are the Risk Factors for Neuronal Intranuclear Inclusion Disease? (Predisposing Factors)

• A positive family history may be an important risk factor, since there are reports of familial Neuronal Intranuclear Inclusion Disease 
• Currently, no other risk factors have been clearly identified for NIID

It is important to note that having a risk factor does not mean that one will get the condition. A risk factor increases one’s chances of getting a condition compared to an individual without the risk factors. Some risk factors are more important than others.

Also, not having a risk factor does not mean that an individual will not get the condition. It is always important to discuss the effect of risk factors with your healthcare provider.

What are the Causes of Neuronal Intranuclear Inclusion Disease? (Etiology)

The genetic cause of Neuronal Intranuclear Inclusion Disease is not currently known.

• Most reported cases are sporadic in nature, with no history of the disorder in an affected individual’s family
• However, there are familial cases also reported in literature. In such cases, an autosomal dominant inheritance is suggested

Autosomal dominant inheritance: Autosomal dominant conditions are traits or disorders that are present when only one copy of the mutation is inherited on a non-sex chromosome. In these types of conditions, the individual has one normal copy and one mutant copy of the gene. The abnormal gene dominates, masking the effects of the correctly function gene. If an individual has an autosomal dominant condition, the chance of passing the abnormal gene on to their offspring is 50%. Children, who do not inherit the abnormal gene, will not develop the condition or pass it on to their offspring.

What are the Signs and Symptoms of Neuronal Intranuclear Inclusion Disease?

The signs and symptoms of Neuronal Intranuclear Inclusion Disease may vary in type and severity among affected individuals, and include:

Very frequently present symptoms in 80-99% of the cases:

• Ataxia 
• Dysarthria
• EMG abnormality

Frequently present symptoms in 30-79% of the cases:

• Abnormal form of the vertebral bodies
• Behavioral abnormality
• Dementia
• EEG abnormality
• EMG abnormality
• Hyperreflexia
• Hypertonia
• Nystagmus
• Ophthalmoplegia
• Scoliosis            
• Seizures
• Spina bifida occulta

Occasionally present symptoms in 5-29% of the cases:

• Abnormality of the pharynx
• Optic atrophy

(Source: Neuronal Intranuclear Inclusion Disease; Genetic and Rare Diseases Information Center (GARD) of National Center for Advancing Translational Sciences (NCATS), USA.)

How is Neuronal Intranuclear Inclusion Disease Diagnosed?

Neuronal Intranuclear Inclusion Disease is diagnosed on the basis of the following information:

• Complete physical examination
• Thorough medical history evaluation
• Assessment of signs and symptoms
• Laboratory tests
• Imaging studies
• Full thickness rectal biopsy 
• Differential diagnosis to rule out other medical conditions that may present with similar signs and symptoms, including spinocerebellar ataxias, progressive juvenile parkinsonism and dystonia

Many clinical conditions may have similar signs and symptoms. Your healthcare provider may perform additional tests to rule out other clinical conditions to arrive at a definitive diagnosis.

What are the possible Complications of Neuronal Intranuclear Inclusion Disease?

The complications of Neuronal Intranuclear Inclusion Disease may include:

• Risk of falls and injury due to seizures
• Severe back pain, if scoliosis is present
• Crowding of organs in the chest cavity and their dysfunction, due to scoliosis
• Loss of speech
• Reduced quality of life

Complications may occur with or without treatment, and in some cases, due to treatment also.

How is Neuronal Intranuclear Inclusion Disease Treated?

There is no cure for Neuronal Intranuclear Inclusion Disease, since it is a genetic condition. The treatment is usually given to manage the signs and symptoms and any complication that develops.

How can Neuronal Intranuclear Inclusion Disease be Prevented?

Currently, Neuronal Intranuclear Inclusion Disease may not be preventable, since it is a genetic disorder.

• If there is a family history of the condition, then genetic counseling will help assess risks, before planning for a child
• Active research is currently being performed to explore the possibilities for treatment and prevention of inherited and acquired genetic disorders

Regular medical screening at periodic intervals with tests and physical examinations are recommended.

What is the Prognosis of Neuronal Intranuclear Inclusion Disease? (Outcomes/Resolutions)

• The prognosis of Neuronal Intranuclear Inclusion Disease is guarded. Although the disease progression is slow, it is ultimately fatal
• Individuals diagnosed with NIID are known to succumb to the condition within 20 years

Additional and Relevant Useful Information for Neuronal Intranuclear Inclusion Disease:

The following DoveMed website link is a useful resource for additional information:

http://www.dovemed.com/diseases-conditions/rare-disorders/