Neurological symptoms can manifest at anytime from the early-infantile period onwards.
The films presenting NP-C neurological symptoms have been developed and produced by:
Dr Nicholas Smith, Paediatric Neurologist-Neurometabolic Diseases, Department of Medicine, University of Cambridge and Mrs Jackie Imrie, Clinical Nurse Specialist in Niemann-Pick disease, Royal Manchester Children's hospital, with the assistance of Professor JE Wraith, St. Mary's Hospital, Manchester and the generous support of the featured patients and their families.
Vertical supranuclear gaze palsy (VSGP) is considered to be a very strong predictor of NP-C, as it is a common symptom and occurs during the entire disease history. Patients have difficulty with spontaneous up and down eye movements, along with saccadic palsy or paralysis. This symptom can become apparent when patients are walking up and down stairs, or watching TV, when the patient may tilt their head to see rather than moving their eyes. VSGP is often the earliest neurological finding in NP-C and subsequently, horizontal gaze can be affected.
When examining a patient, it is important to test not only the ability to follow an object that is moved upwards and downwards, but also the ability to spontaneously move the gaze between two objects held fixed by the upper part of the head and at chest level of the patient.
Gelastic cataplexy is defined as episodes of sudden muscular weakness, which can cause the patient to collapse or fall. It can be triggered by emotion, especially laughter. The collapse is temporary and can range from sudden nods of the head to episodes involving the whole body.
Gelastic cataplexy is a strong predictor of NP-C, as it is quite specific to NP-C and rare in the general adult population overall, although it is also seen in patients with narcolepsy. However, this symptom is not very sensitive, as it was only observed in 16% of patients in the observational study.
Dysarthria is speech that is characteristically slurred and irregular, due to an inability to coordinate the muscles of the mouth, thus making the patient hard to understand. Patients with dysarthria may also have difficulty controlling the pitch, loudness, rhythm and voice qualities of their speech.
Dysphagia is difficulty with swallowing, due to problems with the muscles involved. This symptom is typically subtle at onset and is usually most apparent when the patient is swallowing thin fluids. As NP-C progresses, the patient may have difficulty initiating swallowing, with pooling saliva and nasal regurgitation, followed by tracheal aspiration with associated choking and coughing.
Ataxia is a balance disorder that is a common symptom in NP-C. Patients display unsteadiness of gait and problems with walking, due to uncoordinated movements of limbs (when checking gait, ask the patient to walk a straight line and to turn). Other related symptoms include the inability to perform rapid alternating movements. Patients may be noted to be clumsy during childhood, often falling and having difficulty doing activities such as riding a bike or participating in sports. Patients exhibiting clumsiness may also have difficulties performing fine motor tasks such as handwriting or using scissors. (see Ataxia and Dyspraxia videos)
Dystonia is abnormal movements/posture of limbs caused by agonist and antagonist muscles contracting across joints. A first sign is often one foot turning when walking. Dystonia is a poor predictor of NP-C and occurs mainly in patients with late-onset disease.
Hypotonia is low muscle tone due to problems of motor nerve control. There may be a number of different manifestations, including a delay in motor skills, hypermobile or hyperflexible joints, drooling, speech difficulties, poor reflexes, reduced strength and poor posture. Infants with hypotonia may be diagnosed with “floppy infant syndrome”. Hypotonia is a poor predictor of NP-C and is seen in a number of other diseases, but central hypotonia is one of the first neurological symptoms in young children.
“Delayed developmental milestones” is a general term that covers significant and ongoing delays in a child’s development. Developmental delay can occur in many areas, particular with fine and gross motor skills and are a poor predictor of NP-C, as they can occur due to a number of diseases.
Seizures, also known as fits, can occur in a number of diseases and are often associated with epilepsy. With partial seizures, only a localised part of the brain may be involved and the patient may not lose consciousness. Generalised seizures involve both hemispheres of the brain. Seizures are a poor predictor of NP-C.
Spasticity is altered muscle tone performance and patients experience an unusual tightness of their muscles. Spasticity is a poor predictor of NP-C and occurs in many neurological disorders.
Muscle twitches that are caused by sudden muscle contractions. They can occur alone, in sequence, or in patterns and may occur frequently, or several times per minute. Myoclonus is present in several nervous system disorders including multiple sclerosis, Parkinson’s disease and Alzheimer’s disease and is generally a poor predictor of NP-C. Patients who experience myoclonus may already exhibit other neurological deterioration.