neuronal intranuclear inclusion disease

Neuronal Intranuclear Inclusion Disease (NIID) Description

Neuronal intranuclear inclusion disease (NIID) is a rare and slowly progressive neurodegenerative disorder characterized by the accumulation of eosinophilic hyaline inclusions within neuronal cells. This condition can affect any part of the nervous system, including the central and peripheral nervous systems [2][3].

The most prominent initial symptom in sporadic NIID cases is dementia, followed by other symptoms such as miosis (pupil constriction), ataxia (loss of coordination), and cognitive decline [5]. The disease progression can vary widely among individuals, with some experiencing a slow and gradual decline over several years.

NIID is considered an autosomal dominant disorder, meaning that a single copy of the mutated gene is sufficient to cause the condition. However, the exact genetic mechanisms underlying NIID are not yet fully understood [3].

The presence of eosinophilic hyaline inclusions within neuronal cells is a hallmark feature of NIID. These inclusions can be found in various parts of the nervous system and are thought to contribute to the disease's pathophysiology.

Overall, NIID is a rare and complex neurodegenerative disorder that requires further research to fully understand its underlying mechanisms and potential treatment options.

References:

[1] H Tai (2023) - Neuronal intranuclear inclusion disease (NIID): A progressive neurodegenerative disease characterized by pathologic eosinophilic hyaline inclusions. [2] Neuronal intranuclear inclusion disease (NIID): A slowly progressive, neurodegenerative disease that may affect any part of the nervous system. [3] Neuronal intranuclear inclusion disease (NIID): An autosomal dominant, slowly progressive neurodegenerative disorder characterized by a wide range of symptoms. [4] X Chi (2020) - NIID is regarded as a heterogeneous disease with dementia being the most prominent initial symptom in sporadic cases. [5] JR Kwan (2023) - Neuronal intranuclear inclusion disease is characterised by eosinophilic hyaline intranuclear inclusions in neuronal and somatic cells.

Common Neurological Signs

The most common neurological signs of neuronal intranuclear inclusion disease (NIID) include:

• Ataxia [1]
• Extra-pyramidal signs, such as tremor and oculogyral crises [1]
• Lower motor neuron findings, including absent deep tendon reflexes [1]

Clinical Features

In addition to neurological signs, NIID can also present with various clinical features, including:

• Abnormality of the cardiovascular system, leading to syncope
• Abnormality of the digestive system, resulting in episodic vomiting
• Abnormality of the eye, manifesting as miosis [2]

Other Common Manifestations

According to recent studies, other common manifestations of NIID include:

• Parkinsonism (24.7%) [3]
• Cerebellar ataxia (17.0%) [3]
• Vision loss (14.3%) [3]
• Somatosensory disturbances (10.8%) [3]

Paroxysmal Symptoms and Autonomic Dysfunction

A significant proportion of patients with NIID experience paroxysmal symptoms (66.8%), autonomic dysfunction (64.0%), movement disorders (50.2%), cognitive impairment (49.4%), and other related symptoms [5].

Mental Symptoms

Some patients may also exhibit mental symptoms, such as gibberish, irrational talk, impaired mental attention, without apparent hallucinations and delusions [7].

Clinical Presentation

The clinical presentation of NIID can include pyramidal tract signs, extrapyramidal signs including parkinsonism, abnormal ocular movements, and oculogyric crises [8].

References:

[1] Context result 1 [2] Context result 2 [3] Context result 3 [5] Context result 5 [7] Context result 7 [8] Context result 8

Diagnostic Tests for Neuronal Intranuclear Inclusion Disease (NIID)

Neuronal intranuclear inclusion disease (NIID) is a rare and complex neurological disorder, and its diagnosis can be challenging. However, several diagnostic tests have been developed to aid in the identification of this condition.

• Skin Biopsy: A skin biopsy is a useful diagnostic tool for NIID. It involves taking a small sample of skin tissue from the patient, which is then examined under a microscope for the presence of intranuclear inclusions (1). These inclusions are characteristic of NIID and can be labeled with antibodies for ubiquitin, SUMO1, and p62 (2).
• Diffusion-Weighted Imaging (DWI): Abnormally high signals on DWI along the corticomedullary junction are a useful diagnostic indicator for patients with adult-onset NIID (3). This imaging technique can help identify the presence of NIID in patients.
• Magnetic Resonance Imaging (MRI): MRI signals, particularly those showing high-intensity signals in the brain, can be indicative of NIID (4). However, these findings should be interpreted in conjunction with other diagnostic tests and clinical manifestations.
• Genetic Tests: Genetic tests can also aid in the diagnosis of NIID. These tests can identify genetic mutations associated with the disease (5).
• Cerebrospinal Fluid (CSF) Examination: A CSF examination may show normal pressure, a normal white blood cell count, and slightly elevated protein and glucose levels (6). However, these findings are not specific to NIID.
• Electromyography (EMG): EMG can indicate peripheral nerve degeneration in patients with NIID (7).

It is essential to note that the diagnosis of NIID often requires a combination of clinical manifestations, imaging studies, and laboratory tests. A comprehensive evaluation by a qualified healthcare professional is necessary for an accurate diagnosis.

References:

(1) H Tai et al., Skin biopsy is useful for the antemortem diagnosis of neuronal intranuclear inclusion disease (2023)

(2) S Suthiphosuwan et al., Another diagnostic tool is skin biopsy, which reveals intranuclear inclusions that can be labeled with antibodies for ubiquitin, SUMO1, and p62 (2019)

(3) Y Wang et al., Abnormally high signals of diffusion-weighted image (DWI) along the corticomedullary junction are a useful diagnostic indicator for patients with adult-onset NIID (2020)

(4) Y Liu et al., The diagnosis of NIID can be considered from typical MRI signals, clinical manifestations, pathology of NIIs, and genetic tests (2022)

(5) J Sone et al., The diagnosis of NIID was made histopathologically by autopsy in five cases and by skin biopsy in the other cases (2016)

(6) X Chi et al., A cerebrospinal fluid (CSF) examination indicated normal pressure, a normal white blood cell count, and slightly elevated protein and glucose levels (2020)

(7) WP Deng et al., Electromyography (EMG) indicated peripheral nerve degeneration. Neuropsychological testing showed memory loss (2021)

Current Status of Drug Treatment for Neuronal Intranuclear Inclusion Disease (NIID)

Unfortunately, there is no established effective treatment for NIID that can slow down or halt the progression of the disease. However, symptomatic treatments may be used to improve the quality of life for patients.

• Medications: Some studies have explored the use of medications such as methylprednisolone pulse therapy [2], but these have not been shown to be effective in slowing down the progression of NIID.
• Nutritional Support and Anti-infection Treatment: In some cases, nutritional support and anti-infection treatment may be administered to manage symptoms and prevent complications [4].
• Symptomatic Relief: The primary focus of therapy for NIID is on symptomatic relief, with no established evidence for effective treatment strategies [9].

It's essential to note that the management and treatment of NIID are still evolving, and more research is needed to develop effective treatments.

References:

[2] Han et al. (2021) - An NIID patient was given methylprednisolone pulse therapy (500 mg/daily) for three consecutive days, but this did not slow down the progression of the disease.

[4] Lou (2022) - Nutritional support and anti-infection treatment were administered to a patient with NIID, but there is no established evidence for their effectiveness in slowing down the progression of the disease.

[9] Feng (2024) - There is currently no established evidence for effective treatment strategies for NIID, and symptomatic relief remains the primary focus of therapy.

Differential Diagnosis of Neuronal Intranuclear Inclusion Disease (NIID)

Neuronal intranuclear inclusion disease (NIID) is a complex neurological disorder that requires careful differential diagnosis to rule out other conditions with similar symptoms. The following are some of the key differentials to consider:

• Juvenile Parkinsonism: This condition, also known as juvenile-onset Parkinson's disease, presents with similar motor symptoms to NIID, including tremors, rigidity, and bradykinesia [2].
• Spinocerebellar Degeneration: This degenerative disorder affects the cerebellum and spinal cord, leading to ataxia, dysarthria, and other coordination problems, which can be mistaken for NIID symptoms [3].
• GM2 Gangliosidosis: This rare genetic disorder causes progressive neurological deterioration, including seizures, muscle weakness, and cognitive decline, which can overlap with NIID symptoms [4].

Key Features to Consider

When differentiating NIID from other conditions, the following features are particularly important:

• Imaging characteristics: NIID is characterized by specific imaging findings, such as symmetrical hyperintensity in the basal ganglia on T2-weighted MRI scans [5].
• Clinical manifestations: NIID presents with a range of symptoms, including cognitive decline, seizures, and motor dysfunction, which can be similar to other neurodegenerative disorders [6].
• Genetic factors: NIID has been linked to genetic mutations in some cases, which can help differentiate it from other conditions [7].

Diagnostic Tools

Several diagnostic tools can aid in the differential diagnosis of NIID:

• Skin biopsy: This minimally invasive procedure can provide valuable information for diagnosing NIID and differentiating it from other conditions [8].
• Imaging studies: Advanced imaging techniques, such as MRI and CT scans, can help identify characteristic features of NIID and rule out other conditions [9].

References

[1] Suthiphosuwan, S. (2019). Other differentials to consider would be seizure-induced signal changes, toxic leukoencephalopathies, inherited leukodystrophies, and neurodegenerative disease... [1]

[2] Nov 23, 2023 — Differential diagnosis. Clinically the differential diagnosis includes juvenile parkinsonism · spinocerebellar degeneration · GM2 gangliosidosis [2]

[3] by Y Liu · 2022 · Cited by 24 — Differential diagnosis of neuronal intranuclear inclusion disease... [4]

[5] by M Furuta · 2023 · Cited by 2 — Neuronal intranuclear inclusion disease (NIID) is a clinically complex neurological disorder that appears sporadically or autosomally. [5]

[6] by J Sone · 2016 · Cited by 341 — We should take NIID into account for differential diagnosis of leukoencephalopathy and neuropathy... [6]

[7] by C Mao · 2022 · Cited by 8 — Neuronal Intranuclear Inclusion Disease (NIID) is a degenerative disease with heterogeneous clinical manifestations. [7]

[8] by M Motoki · 2018 · Cited by 24 — Neuronal intranuclear inclusion disease (NIID) is a slowly progressive neurodegenerative disorder characterized by eosinophilic hyaline inclusions in... [8]

[9] by J Sone · 2011 · Cited by 204 — Skin biopsy is an effective and less invasive antemortem diagnostic tool for NIID. [9]