Additional information

Sodium channel disorders: Abnormalities in the structure and/or function of the sodium channel can lead to channelopathies leading to diseases like epilepsy, hyperkalemic periodic paralysis, Brugada syndrome, cerebellar ataxia, anosmia, atrial fibrillation, sudden infant death syndrome, long QT syndrome, erythromelalgia and pain syndromes.

Pheochromocytoma: It is a tumor arising from the chromaffin cells of the adrenal medulla. Normally, epinephrine is the major output of the chromaffin cells, but in pheochromocytoma, the tumor produces mainly NE with or without epinephrine. However, in extra-adrenal pheochromocytomas only NE is produced.

Signs of cerebellar lesions: Lesions in the cerebellum manifest as ipsilateral signs of cerebellar ataxia, dysdiadochokinesia, dysmetria, intention tremors and negative Romberg sign. Cerebellar ataxia is due to lack of coordination of movements. In dysdiadochokinesia the patient is unable to perform rapidly alternating movements like pronation and supination. Intention tremors start at the initiation of voluntary motor activity like moving a hand to pick up an object and increase in amplitude as the target approaches or at the end of movement. Rebound phenomenon is seen where the patient is unable to stop a motion as antagonistic muscles are weakened. It is tested by the Holmes-Stewart manoeuvre by flexing the arm against resistance. Dysmetria is a condition in which there is improper measuring of distance in muscular acts; hypermetria is overreaching (overstepping) and hypometria is underreaching (understepping). It is tested by the finger-nose test.

Two noteworthy points - I) Nigrostriatal pathway of substantia nigra is pro-movement. II) Internal segment of globus pallidus is key - inhibit it to initiate movement and activate it to reduce movement (internal segment is anti-movement).

The following areas receive direct visual inputs (apart from the visual pathway)

1. The suprachiasmatic nucleus: It regulates circadian rhythms depending on environmental light.
2. The pretectal nuclei: Role in pupillary light reflex.
3. Superior colliculus: Role in conjugate gaze movements.

Amacrine cells and horizontal cells: Amacrine cells are interneurons in the retina. They receive inputs from the bipolar cells and relay to the ganglion cells. They have short branching dendrites and secrete a variety of neurotransmitters including glycine and GABA. Amacrine cells are involved in the detection of motion, speed and changes in the intensity of light. Horizontal cells are inhibitory neurons and connect to rods and cones. They help to enhance contrast.

Caloric testing and physiological nystagmus: Caloric testing is also known as Barany’s test or doll’s eye movements. When the head is turned e.g. to the right, there is increased firing rate in the right sided vestibular nerve and decreased firing rate in the left vestibular nerve. Normally, assuming the brainstem and vestibular system is functioning efficiently, this causes physiological nystagmus (vestibulo-ocular reflex). In physiological nystagmus, the eyes initially move away from the direction of rotation called as slow phase of nystagmus. This is followed by rapid correction so that the eyes move towards the direction that the head was turned, called the rapid phase of nystagmus.

The caloric test is used to assess brainstem functioning in comatose patients. The head of the patient is raised by about 30 degrees which helps to orient the horizontal semicircular canal in a vertical plane. The test includes the insertion of cold or warm water into the ear. This produces convection currents in the endolymph, ultimately leading to stimulation of the hair cells. When the ear is irrigated with cold water it induces a nystagmus with a slow phase towards the irrigated ear and a fast phase directed away from it. When warm water is irrigated, the fast phase of nystagmus is directed towards the irrigated ear. Remember the mnemonic COWS (cold opposite warm same) to remember the direction of the fast phase. The firing rate of the vestibular nerve will increase in response to warm water and decrease in response to cold water.

Weaker reflex in one eye suggests tumors of the VIII cranial nerve, vestibular neuronitis, Meniere’s diseases, migraine and stroke. Cerebellar lesions, especially in the flocculus, cause exaggerated nystagmus in caloric testing. This can be seen in multiple sclerosis, ingestion of psychoactive drugs and anxiety. Bilaterally decreased caloric response is seen in neurosyphilis, neurodegenerative diseases, intracranial hypertension, Wernicke-Korsakoff syndrome etc. Absent caloric response is seen in hair cell damage like in aminoglycoside toxicity, vestibular nerve damage and brainstem damage.