Continuing Education Activity

Arnold-Chiari 1 malformation, otherwise known as the Chiari 1 malformation, is the more common variant of the Chiari malformations, defined as a spectrum of hindbrain abnormalities involving the cerebellum, brainstem, skull base, and cervical cord. It is characterized by the caudal descent of the cerebellar tonsils through the foramen magnum. This activity reviews the key findings seen in the Chiari 1 malformation with workup recommendations regarding key investigations and further management.

Objectives:

• Identify the etiology of the Chiari 1 malformation.
• Outline the appropriate evaluation of a Chiari 1 malformation.
• Review the appropriate investigations, treatments and management options available for a Chiari 1 malformation.
• Describe team strategies for improving care coordination and communication to advance Chiari 1 malformations and improve outcomes.

Introduction

At the end of the nineteenth century, two pathologists, Julius Arnold (1835-1915) and Hans Chiari (1851-1916), described a complex clinical and pathological condition involving deformity of the cerebellum and brainstem, in children. Chiari malformations are now defined as a spectrum of hindbrain abnormalities involving the cerebellum, brainstem, skull base, and cervical cord. According to the type of herniation of the brain tissue displaced in the spinal canal, and the characteristics of the anomalies of the development of the brain or the spine, four types of Chiari malformations (types I to IV) are classified. Together with basilar invaginations, Chiari malformations represent the most common craniocervical junction malformations seen in adults.

Among Chiari malformations, Arnold-Chiari I malformation, otherwise known as the Chiari type I malformation, is the more common variant. It is characterized by the caudal descent of the cerebellar tonsils through the foramen magnum.[1] However, there is no accepted universal definition amongst clinicians as the malformation shows incongruity in clinic radiological correlation.[2] Some authors, for example, have recently proposed to define the Chiari type I malformation as 'Chiari syndrome,' while the term malformation should be reserved for types II-III.[3] Clinically, Chiari malformation type I can be asymptomatic ('hindbrain hernia') or manifests itself in late childhood or adulthood with tussive headaches and focal neurological manifestations. On the other hand, type II, III, and IV are congenital and clinically important. The nosographic collocation of type 0 or 0.5 Chiari malformation or 'Chiari like' (symptoms without tonsillar herniation), type 1.5 Chiari malformation (intermediate between type I and II), and complex Chiari is controversial and not universally accepted.

Etiology

Chiari type I malformation can have a genetic basis or can be secondary to different conditions involving alterations in the basal skull such as craniosynostosis, craniocerebral disproportion, platybasia, secondary neurulation abnormalities, bone metabolic disorders. This type of malformation can be the result of a build-up of pressure in the brain produced, for instance, by hydrocephalus or a tumor. Furthermore, iatrogenic Chiari I, due to lumboperitoneal shunt for treatment of idiopathic intracranial hypertension has also been reported.[4] An injury-related Chiari I type is a rare but possible condition.

In some cases, it is also possible that a traction mechanism from below is the cause of the disease. According to a mechanisms of caudal traction (tethered cord), indeed, the lowering of the tonsils in Arnold Chiari type I could be provoked by a traction by the filum terminal (between the coccyx and the sacral part of the vertebral column), that pulls from the bone marrow and brainstem structures, causing, in turn, the descent of the cerebellar tonsils.[5]

When a genetic basis can be suggested, links to chromosomes 2, 9, 14, and 15 have been proposed.[6][7][8] For instance, a mutation in the NKX2-1 gene (14q13.3) that provides instructions for making the protein Nkx-2.1, a member of the homeobox protein family involved in the formation of body structures such as forebrain during early embryonic development, has been recently identified, in a girl affected by Chiari type I.[9] Another potential mutation can involve EPAS1 (2p21) encoding the hypoxia-inducible factor 2-alpha (HIF-2-alpha) that is the major regulator of erythropoietin and is implicated in the endochondral and intramembranous ossification.[10] These genetic disorders probably induce an impairment of the development of the para-axial mesoderm with herniation of the cerebellar tonsils, resulting in a small posterior fossa and crowded foramen magnum. This is consistent with a proposed association with other mesodermal connective tissue disorders, for example, Ehlers-Danlos syndrome [11], although the relationship between this condition and Chiari I is still unclear. Researchers from the Italian neurological Carlo Besta Institute, have recently dissected different pathways (e.g., disorders of the RAS/MAPK pathway) that can be found altered in both Chiari I malformation and defined genetic syndromes.[12] Despite these data, the genetics of the Chiari I malformation needs more confirmation.[13]

Epidemiology

Chiari type I is the most common Chiari malformation. It is estimated to occur in approximately every 1 in 1000 births, with a slight female: male predominance of 1.3 to 1.[14] Probably, the epidemiological data is underestimated, since many forms are paucisymptomatic and manifest themselves clinically only in adulthood. Indeed, neuroimaging data suggest that the clinical condition may be more frequent, with an estimated prevalence of 1% in the pediatric population.[15][16]

Pathophysiology

Chiari malformation type I is described according to the morphology of the hindbrain. Classic features are a greater than 5 mm descent of the caudal tip of cerebellar tonsils past the foramen magnum; however, as little as less than 3 mm caudal cerebellar descent may be seen in a child presenting early with Chiari I.[17][18][19][20] Of note, there is no an associated herniation of the brainstem and spina bifida that characterize Chiari type II, or classic Chiari malformation; severe protrusion or herniation of the cerebellum and brainstem involving serious consequences on the development of the nervous system (type III); or incomplete or undeveloped cerebellum with structural alterations of the skull and spinal cord (type IV).

In Chiari type I, the main cause of pathology is due to tonsillar invagination and direct compression of neurological structures within the foramen magnum/upper spinal cord, with obstruction of cerebrospinal fluid (CSF) and potentially associated syringomyelia. This latter malformation, also termed as Morvan disease, is myelopathy that consists of the abnormal formation of one or more cysts or cavities (syrinxes) containing CSF inside the spinal cord and is detectable in 20% to 85% of Chiari I cases. Secondary features by way of syrinx formation may be further obstruction of spinal canal CSF outflow and further direct compression of neurovascular structures.[21] Regarding the location of syringomyelia development, the most common region affected is the cervical region, followed by combined cervical and thoracic syringomyelia. The pathogenesis of syringomyelia must be well elucidated. A theory postulates the role of arterial pulsation that could induce a pressure dissociation between the subarachnoid spaces of the cranium and spinal cord. Again, other theories suggest that syrinx may represent the effect of the anatomical defect of the cerebellar tonsils or the consequence of the altered CSF flow.[22] Syringobulbia that communicates with the fourth ventricle has also been described.[23]

Because the foramen of Magendie can be obstructed, the fourth ventricle can result enlarged. Hydrocephalus may occur in approximately 10% of patients. Skeletal associations may include platybasia/basilar invagination, Sprengel deformity, and atlantooccipital assimilation. Syndromic associations include Klippel-Feil, Gorham-Stout disease, Crouzon, and Pfeiffer syndromes.[18] Many of these conditions involve alterations of the basal skull and may themselves be causes of the Chiari malformation.

History and Physical

Patients with Chiari I malformation are asymptomatic. The most common symptom, however, in both the adult and child, is pain or headache in the occipital/cervical region (neck pain) [24]. In the very young population, a history of headache or pain may be difficult to elicit, where these symptoms are more likely to manifest as excessive crying, irritability, and failure to thrive.[19][25]

It should be noted that the headache produced in Chiari I is often exacerbated with the Valsalva maneuver due to the reduced size of the foramen magnum. This should be differentiated from chronic headaches that do not vary with the Valsalva maneuver, which may be attributed to pathologies other than Chiari I, for example, intracranial hypertension.[26][27] Although migraine headaches have a prevalence similar to that of the general population, in individuals affected by Chiari I there is an earlier age of onset and a severe clinical presentation.[28]

Apart from headache and pain, a wide spectrum of clinical manifestations may characterize the malformation. In particular, signs and symptoms are mainly due to direct brainstem compression that may cause autonomic dysfunction.[29][30] Other signs, such as scoliosis, are structural. Clinical features may include[29][30][31][24][32][33][34]:

• Syncopal episodes and sinus bradycardia due to autonomic dysfunction
• Swallowing alterations and vomiting
• Balance difficulties with an unsteady gait 
• Problems in hand coordination
• Sensorial manifestations such as numbness and tingling, in the extremities 
• Dizziness
• Tinnitus
• Progressive muscular weakness in the arms and legs is seen, and stiffness in the back, shoulders, arms, or legs, represent clinical manifestations of syringomyelia. Acute paraparesis has been described as case reports. Syringobulbia can produce weakness in the facial muscles.
• Bladder and bowel problems can be the result of syrinx-induced compressive effects.
• Scoliosis, particularly in pediatric patients. Although scoliosis is due to syringomyelia, recent studies suggest that there is no association of syrinx length and holocord syrinx with scoliosis.
• Nystagmus may also manifest in Chiari I with syringobulbia; however, this is a less specific sign.

Adults and children may present with Chiari I differently. For example, pediatric patients are increasingly likely to present with brainstem dysfunction, sleep apnea, or feeding difficulty.[35] The latter is due to the involvement of the glossopharyngeal and vagus nerves resulting in an absent gag reflex and hoarseness.[36] As the cerebellum is involved in higher cognitive functions, potential cognitive alterations have been recently investigated, and the presence of a generalized cognitive impairment in the executive functioning, verbal fluency, spatial cognition, language, and memory processing, has been reported.[37]  

Evaluation

Neuroimaging

Magnetic resonance imaging (MRI) is the main investigation performed for Chiari type I malformation, providing a depiction of craniocervical junction anatomy with identification of secondary complications such as hydrocephalus or syringomyelia.[38]

When the patient is unable to undergo MRI scanning, other methods investigations to explore include CT myelography, non-contrast CT, and radiographs of the head and neck.

On MRI, as well as tonsillar descent, there may be an appearance of ‘peg-like’ or pointed tonsils, seen in both symptomatic and asymptomatic individuals.[39] Other associations include a cervicomedullary ‘kink,’ seen in up to 71% of symptomatic patients.[40] In general, the greater the degree of cerebellar tonsil descent, the greater the likelihood the patient is symptomatic.[18]  

Patients who have incidental tonsillar ectopia without symptoms may benefit from MRI cine CSF flow studies. Positive findings on CSF flow include pulsatile systolic tonsillar descent and CSF flow obstruction at the level of the foramen magnum. These findings can provide further information to help assess whether the patient may benefit from surgery.[41] 

Laboratory Studies

Laboratory studies are not used for the diagnosis of Chiari I. However, any preoperative workup requires appropriate baseline investigations including full blood counts, electrolytes and metabolites; alongside a chest radiograph and electrocardiogram (ECG). 

 Other useful tests may include:

• Sleep study: Involves sleeping overnight in a room where they can monitor breathing, snoring, oxygenation, and seizure activity to determine if there is any evidence of sleep apnea.

• Swallowing study: Fluoroscopy used to watch the internal swallowing process to determine if there is an abnormality suggestive of lower brainstem dysfunction. 

• Brainstem auditory evoked potential (BAER): It is an electrical test to examine the function of the hearing apparatus and brainstem connections. This is used to determine if the brainstem is working properly.

• Somatosensory evoked potentials (SSEP): An electrical test of the nerves involved in sensation, which gives some information about peripheral nerve, spinal cord, and brain function.

Prenatal diagnosis of Chiari type I malformation, and syringomyelia has also been described.[42]

Treatment / Management

Because there is no clear consensus about the precise algorithm for the management of Chiari type I malformation, its treatment remains rather empirical. It encompasses a combination of medical and surgical approaches through a multimodal dynamic strategy. 

Medical therapy

Medical management in Chiari I is limited and generally confined to symptomatology (e.g., headaches or neck pain). Non-steroidal anti-inflammatory drugs (NSAIDs), muscle relaxants, and physical support collars may provide symptomatic relief. However, these options provide little improvement of less common symptoms, for example, gait disturbance. Meditation, yoga, or mindfulness therapy have also been proposed for addressing pain.  

Surgical strategies

Surgical treatment is typically reserved for patients who present with severe or worsening symptoms who go on to have a confirmation of cerebellar descent on imaging and a Chiari malformation obstructing CSF flow confirmed by cine MRI. Surgery aims to provide decompression of the restricted cervicomedullary junction, allowing CSF flow to be restored to optimal levels. The main approach involves performing a suboccipital craniectomy at the level of the C1 posterior arch (C1/2 laminectomy), with or without associated duroplasty.[43] Thus, this intervention, indicated as posterior fossa decompression (PFD), is the most adopted neurosurgical approach focused on restoring CSF flow across the foramen magnum. The procedure is performed in up to 99% of the literature.[44] A minimally invasive procedure allowing resection of submeningeal cerebellar tonsillar herniation followed by reconstruction of Cisterna magna without craniectomy has been proposed for addressing Chiari I with syringomyelia.[45] Of note, cine MRI has been proposed for guiding the intraoperative decision to realize duraplasty during PFD.[46] Among non-invasive approaches, several methods have also been proposed to decompress syringomyelia with distal drainage to the subarachnoid space (syringosubarachnoid shunt).[47]

Differential Diagnosis

Important diagnoses to consider in the workup of Chiari I are:

• Incidental tonsillar ectopia (less than 5 mm)
• Chiari II to IV types
• Idiopathic intracranial hypertension (pseudotumor cerebri)
• Craniospinal hypotension
• Basilar invagination

Prognosis

Surgical outcomes are favorable, with 73% of patients improving less than 1-year postoperatively and 79% at 1 to 3 years at follow-up.[48] PFD induced symptom improvement in about two-thirds of individuals, especially in those without associated syringomyelia.[49]

Complications

The most common postoperative complications are CSF leakage and pseudomeningocele formation.[50][24] The latter may require revision surgery or shunt insertion.[51] Other complications include aseptic and bacterial meningitis, vertebral artery injury, and epidural hematoma formation.[52] Concerning the type of surgical approach, in a retrospective analysis, Farber et al. found that meningitis occurred especially in decompression and duraplasty performed using bovine pericardial xenograft compared with the allograft method.[53]

Postoperative and Rehabilitation Care

Postoperatively patients may experience headache and neck pain due to the operation. Neck exercises may be given to aid the return of full mobility as soon as it is able.

Patients typically return to work in 4 to 6 weeks, with a follow-up MRI performed at around 6 months to 1 year.

Full recovery from Chiari surgery may take months or longer. It is important to slowly increase activity in a graded manner, avoiding any strenuous lifting in the early phase of recovery.

Deterrence and Patient Education

While nothing can be done to prevent congenital Chiari type I malformation, patient education plays a large role in familiarising not only the patient about the signs and symptoms of the condition but also helping increase awareness of the close family, friends, and carers who may spend significant periods with the patient.

Pearls and Other Issues

• The Chiari I malformation is the most common of the Chiari manifestations resulting in hindbrain abnormality. 
• While the genetics origin of the malformation requires more confirmation, the malformation can occur in several defined genetic syndromes.
• Many patients can be asymptomatic or paucisymptomatic, and the malformation is diagnosed more commonly in adolescents or adults.
• Patients may present with symptoms of occipital pain or chronic headache; however, they may also present with less specific symptoms such as swallow impairment or sleep apnea.
• MRI is the main investigation of choice in these individuals, allowing full visualization of the cervicomedullary junction. 
• Because algorithms for the management of the Chiari type I are not well-established, a combination of medical and surgical approaches through a multimodal dynamic strategy is mandatory.
• Surgical decompression is performed in symptomatic individuals with success, often significantly alleviating the patients presenting symptomatology and restoring full neurological function.

Enhancing Healthcare Team Outcomes

The Chiari type I malformation is a rare developmental disorder that is best managed by an interprofessional team that includes a neurologist, pediatrician, surgeon, social worker, nurse, and physical therapist. These patients tend to have many physical and functional limitations, including impairment of swallowing, speaking, and even walking.

While the prognosis for most patients is good, when clinically suspected, appropriate investigations should be performed promptly to facilitate an appropriate level of treatment (e.g.conservative vs. surgical) and, in turn, to prevent future deterioration.