IVD of Neurology
What are Neurological Diseases
Neurological conditions involve a vast spectrum of diseases affecting the brain, spinal cord and peripheral nerves. These disorders are the result of structural, biochemical or electrical changes to the nervous system that cause a range of symptoms. There are various neurological diseases with different causes, symptoms and, and progression.
Types of Neurological Diseases
We can categorise neurological conditions into a number of different kinds depending on their cause and location in the nervous system.
Neurodegenerative Diseases: It is a condition in which neurons are gradually degenerating, reducing cognitive and motor function. Typical examples are Alzheimer's disease, Parkinson's disease and Huntington's disease.
Cerebrovascular Diseases: These are conditions that impact the blood vessels supplying the brain, such as stroke and transient ischemic attacks.
Demyelinating Diseases: Diseases such as multiple sclerosis are examples of this type of disease, which results in destruction of the layer of myelin that surrounds nerve fibers.
Infections: Diseases like meningitis and encephalitis arise from bacteria, viruses or fungi causing infection in the nervous system.
Seizure Disorders: The most common type is epilepsy, where the brain develops abnormal electrical activity that can cause seizures.
Headache Disorders: Chronic diseases such as migraines and cluster headaches can drastically influence quality of life.
Movement Disorders: Beyond Parkinson's disease, this category includes essential tremor and dystonia.
Fig1. General pathophysiological mechanisms of neurodegenerative diseases. (Corneliu Toader, et al. 2023)Symptoms of Neurological Diseases
The symptoms of neurological diseases vary widely depending on the specific disorder and the affected region of the nervous system.
- Muscle weakness or loss of sensation
- Partial or complete paralysis
- Seizures or convulsions
- Difficulty in speaking, reading, or writing
- Memory loss or cognitive decline
- Unsteady gait or loss of coordination
- Visual disturbances
- Chronic pain
Causes of Neurological Diseases
Genetic Factors: Many neurological disorders such as Huntington's disease and some epilepsy have a genetic component.
Infections: Pathogens such as bacteria, viruses, and fungi can attack the nervous system and cause symptoms like meningitis and encephalitis.
Environmental Factors: Toxins, chemicals and heavy metals can cause damage to the nervous system.
Trauma: Spinal cord injuries, traumatic brain injuries, and accidents can lead to neurological disorders.
Autoimmune Disorders: Diseases like multiple sclerosis occur when the immune system mistakenly attacks the nervous system.
Nutritional Deficiencies: Insufficient vitamins, vitamin B12 for example, can cause neurological disorders.
Biomarkers of Neurological Diseases
Biomarkers are measurable indicators of a biological condition and can be used to detect or monitor neurological diseases. They are critical to unravelling the disease processes, early diagnosis, and therapeutic response. The most frequently researched biomarkers in neurological disorders include:
Genetic Markers: Genetic variation in certain genes can be used to predict people prone to certain neurological disorders.
Proteins: Abnormal levels of proteins, such as amyloid-beta in Alzheimer's disease, can indicate the presence of disease.
Neuroimaging: Imaging studies such as MRI and PET scans can reveal structural abnormalities in the brain in cases of neurological disorders.
Biochemical Markers: Chemical changes in the cerebrospinal fluid or blood are predictors of neurodegenerative disorders.
Electrophysiological Markers: EEG and EMG tests measure electrical activity in the brain and muscles to diagnose seizure disorders and neuropathies.
Detection of Neurodegenerative Disease Using Biomarkers
Identifying neurodegenerative disorders using biomarkers has advanced considerably, enabling early diagnosis and progression.
MRI and PET Imaging: These imaging tools help detect alteration in brain structure and function. For example, PET scans can detect amyloid plaques in Alzheimer's patients long before they produce symptoms.
Cerebrospinal Fluid Analysis: From cerebrospinal fluid, doctors can detect biomarkers such as tau proteins and amyloid-beta, a precursor to disorders such as Alzheimer's.
Blood Tests: Recent studies aim to find blood biomarkers that may offer a less invasive diagnostic approach.
Genetic Testing: Detecting genetic mutations of disease, such as familial Alzheimer's, can assess risk and provide early intervention.
Biochemical Assays: These test can measure concentrations of specific proteins or metabolites related to neurodegenerative disease.
These approaches, though highly promising, are always being developed to increase sensitivity, specificity and usability.
Case Study
Case 1: Palmqvist S, Janelidze S, Quiroz YT, et al. Discriminative Accuracy of Plasma Phospho-tau217 for Alzheimer Disease vs Other Neurodegenerative Disorders. JAMA. 2020 Aug 25;324(8):772-781. doi: 10.1001/jama.2020.12134. PMID: 32722745; PMCID: PMC7388060.
There are limitations in current diagnostic testing approaches for Alzheimer disease (AD). This study is to examine plasma tau phosphorylated at threonine 217 (P-tau217) as a diagnostic biomarker for AD.
Fig2. Plasma P-tau217 Concentrations in the Neuropathology Cohort (Cohort 1) A, Correlations between plasma tau phosphorylated at threonine 217 (P-tau217) concentration and total tangle density score in the Alzheimer disease (AD; National Institute on Aging–Reagan Institute [NIA-RI] intermediate or high likelihood of AD) and non-AD (no or sparse β-amyloid plaques) groups.Case 2: Datta D, Gopinadhan A, Soto A, Bangirana P, Opoka RO, Conroy AL, Saykin AJ, Kawata K, John CC. Blood biomarkers of neuronal injury in paediatric cerebral malaria and severe malarial anaemia. Brain Commun. 2023 Nov 27;5(6):fcad323. doi: 10.1093/braincomms/fcad323. PMID: 38075948; PMCID: PMC10710298.
Persistent neurodisability is a known complication in paediatric survivors of cerebral malaria and severe malarial anaemia. Tau, ubiquitin C-terminal hydrolase-L1, neurofilament-light chain, and glial fibrillary acidic protein have proven utility as biomarkers that predict adverse neurologic outcomes in adult and paediatric disorders.
Fig3. Levels of and correlation between CNS biomarkers. (A) Admission plasma biomarker concentration by study group. Dots represent biomarker concentrations (pg/mL) in individual children and solid lines show median concentrations and interquartile range. (B) Correlation between biomarkers and plasma tau (previously tested). Numbers within in boxes depict Spearman's correlation coefficients.