Neurological Symptoms of Mast Cell Activation Syndrome

Mast Cell Activation Syndrome (MCAS) is an immune mediated disease wherein the release of mast cell chemical mediators lead to heterogenous multisystemic inflammatory and allergic presentations (Weinstock, 2023). Neurological symptoms associated with MCAS are sometimes profound and debilitating but there is a relative dearth of literature exploring these symptoms. Many of these neurological symptoms can improve with treatment so it is important they are recognised and managed in a timely manner.

Some common neurological symptoms associated with MCAS include headaches, syncopal attacks, acute back pain, anoxic encephalopathy, seizures, transient chorea (Smith, Butterfield, Pardanani, DeLuca, & Cutrer, 2011), vertigo, paraesthesia, chronic inflammatory demyelinating polyneuropathy, monoclonal gammopathy of unknown significance and subacute combined degeneration (Klimas, 2014). There may also be psychiatric and cognitive symptoms including depression, cognitive dysfunction, generalized anxiety, panic attacks, and sleep disturbances (Weinstock, 2023).

Unfortunately, there is a paucity of data exploring neurological symptomatology in MCAS. It might therefore be helpful to explore the data available in closely related pathologies. In a retrospective series looking at patients with a formal diagnosis of mastocytosis who presented to a neurologist with nervous system symptoms, they found out that 35% of them reported headaches and 40% of them had complex spells involving syncope (Smith, Butterfield, Pardanani, DeLuca, & Cutrer, 2011). Nine people presented with acute back pain which was ultimately ascribed to vertebral compression fractures and one person had spinal cord compression from a vertebral mast cell infiltrate. It is not currently clear if that individual had a neurologic deficit such as lower limb weakness or a sensory disturbance as a result of the spinal cord compression.

It is also not uncommon for a formal diagnosis of migraine to be made in patients with mast cell activation disorders (MCAD) . It is universally accepted that mast cell degranulation play an important role in the pathogenesis of migraine headaches (Guan, 2023). Dizziness, light-headedness, vertigo and feeling like one is about to faint are also quite common in MCAS and might very well be due to vasodilatory effects of some of the mediators released from mast cells. It is not surprising therefore that some patients suffering with MCAS are often diagnosed in the first instance with dysautonomia or postural orthostatic tachycardia syndrome (POTS). Other proposed mechanisms of dysautonomia include the effects of mediators on the autonomic nervous system and small fibres of peripheral nerves.

Neurophysiologic tests such as nerve conduction studies and electromyography are sometimes abnormal in MCAS and might reflect a possibility of CIDP (Chronic inflammatory demyelinating polyneuropathy). Some of these patients are sometimes also positive for monoclonal gammopathy of unknown significance- a biomarker linked to multiple myeloma. It is however believed the presence of MGUS is as a result of MCAS and not the other way around.

It is not unusual to find some recurring features on neuroimaging in patients with mast cell disorders. In a test cohort of 39 mastocytosis patients with psycho-cognitive symptoms, they found that 49% of them had structural brain abnormalities, especially atypical punctuated white matter abnormalities (Boddaert, et al., 2017). They found out that patients with white matter abnormalities (WMA) showed increased perfusion in the putamen compared with patients without WMAs and with healthy controls. Putamen perfusion was also inversely correlative with depression sub-scores demonstrating, arguably for the first time, a high prevalence of morphological and functional abnormalities in this subset of patients.

Some other patients with MCAS have been diagnosed with subacute combined degeneration (SCD) which is a neurologic pathology associated with B12 deficiency. Some of these patients complain of losing the ability to feel vibrations or lose a sense of where their limbs are in space (proprioception). Considering the commonality of gastric symptomatology in MCAS, it is therefore understandable why sufferers might suffer deficiency of vitamins like B12 which might present with neurologic sequelae.

In conclusion, neurological symptoms might partly or wholly represent the presenting complaints in a patient with MCAS. Indeed, neurologists are often inadvertently asked to evaluate patients with mast cell disease before a formal diagnosis has been made. (Smith et al, 2011)

A lot more work needs to be done in evaluating the neurologic sequelae of MCAS and an understanding of the pathogenesis of this relationship might help bolster our understanding of the underlying pathology in a variety of mast cell diseases.

Oluwaseyi Adebola1 (MBBS, MSc., MRCS)

With thanks to Olufemi SANYAOLU (MBChB, MWACP, MRCP (UK), FMCP) for peer review

1Neurosurgery specialist registrar, Liverpool and Medical Lead for Mast Cell Action, UK


Boddaert, N., Salvador, A., Chandesris, M. O., Lemaître, H., Grévent, D., Gauthier, C., . . . Hermine, O. (2017). Neuroimaging evidence of brain abnormalities in mastocytosis. Translational Psychiatry. Retrieved from

Guan, L. C. (2023). Roles of mast cells and their interactions with the trigeminal nerve in migraine headache. Molecular Pain. doi:

Klimas, L. (2014). Mast Attack. Retrieved from Mast Attack:

Smith, J. H., Butterfield, J. H., Pardanani, A., DeLuca, G. C., & Cutrer, M. F. (2011). Neurologic symptoms and diagnosis in adults with mast cell disease. Clinical Neurology and Neurosurgery, 570-574. doi:

Weinstock, L. B. (2023). Neuropsychiatric Manifestations of Mast Cell Activation Syndrome and Response to Mast-Cell-Directed Treatment: A Case Series. Journal of personalized medicine. doi:

Become a friend

Sign up to become a Friend of Mast Cell Action so we can keep you up to date on our progress and on how to get involved in our latest campaigns and initiatives. 

Become a friend


Mast Cell Action relies entirely on the generosity of people like you. Please make a donation now and together we can make a difference to those affected by MCAS.

Make a donation