Clinical ConsultsWhat’s Your Diagnosis?

Volume 11 | Issue 4 | April 2019

PATIENT HISTORY SIGNALMENT: “Koda” is a 10.5 year old neutered male Akita. Weight 87.5 lb/39.8 kg.

PERTINENT PAST HISTORY: “Koda” has been a healthy dog. He eats commercial dry adult dog food. He is current on recommended vaccinations and receives monthly preventatives. He has no significant travel history. He has a history of a completely excised cutaneous trichoblastoma on his right forelimb. “Koda” suffers from seasonal conjunctivitis which is treated as an allergic manifestation.

CURRENT HISTORY: “Koda’s” owner presented him on emergency for evaluation of difficulty swallowing and drooling excessively. His owner noted he had been drooling more than normal for the past several weeks. He was also having a hard time swallowing both food and water and it seemed as though his tongue wasn’t working well. His owner reported “Koda” seems to spend a long time at the water bowl drinking and there is always a large amount of water on the floor when he is done. It appears that he is biting the water rather than lapping it with his tongue as his tongue seems to be uncoordinated. “Koda” also seems to be spitting up his food when he eats and the owner suspects he is having a hard time swallowing it.

DROOLING AND WEAKNESS—Differentials to Remember

Donna J. Spector , DVM, DACVIM, Internal Medicine

Clinical Note: It is important to differentiate between dysphagia with difficulty prehending and swallowing food as a cause of “spitting food out” or true regurgitation as a cause of “spitting food out.” Upon further investigation in “Koda’s” case, he seemed to be having far more difficulty with prehending and then swallowing food. However, he was noted to regurgitate food well after eating also. The day prior to emergency presentation, “Koda” fell when he got out of the car and the owner noted he has become progressively weaker in his hind limbs. For the past few months, “Koda” has been much more hesitant to jump into the car and the owner has been noticing muscle loss in his pelvic limbs.

The owner reported noticing a broken canine tooth a few weeks ago. He had taken “Koda” to his primary care veterinarian last week when he noticed the excessive drooling thinking it may have been related to the tooth. “Koda’s” primary care veterinarian noted a fractured right maxillary canine tooth and a devitalized left maxillary canine tooth. Drooling hadn’t been noted at the time of the exam. “Koda” was noted to have lost 10 pounds of weight since his last annual examination. Bloodwork was performed in preparation for a dental procedure and revealed a mildly elevated ALT (170 U/L; reference range 10-121 U/L) and mildly elevated CK (471 U/L; reference range 10-200 U/L) but was otherwise unremarkable. Clinical Note: Both of these values (ALT and CK) are muscle enzymes and although only mildly elevated, should have been a red flag to a possible myopathy in a patient presenting with a report of muscle loss, progressive muscle weakness, dysphagia and regurgitation. “Koda” was vaccinated that day against Leptospira, Bordetella and canine influenza. This was 5 days prior to the emergency presentation.

EMERGENCY EXAMINATION “Koda” had a fever with a temperature of 103.2º F. He had moderately loud bronchovesicular sounds on thoracic auscultation and was tachycardic and tachypneic. He had moderate generalized muscle wasting noted but otherwise examination was fairly unremarkable.

Cervical and thoracic radiographs were obtained which revealed a moderate alveolar pattern with air bronchograms in the right middle lung lobe. “Koda” was noted to have a moderate amount of air present within the intrathoracic esophagus, although a specific megaesophagus was not noted. There were no significant findings within the pharyngeal or laryngeal region. The findings were consistent with pneumonia. Aspiration pneumonia was suspected given the patient history of regurgitation and air within the esophageal lumen. “Koda” was discharged to the owner with clavamox (750 mg PO BID) and instructions to nebulize him in a warm steam filled bathroom followed by coupage several times daily. The owner was instructed to follow up with the primary care veterinarian in 3 days.

“Koda” re-presented on emergency within 24 hours for severe coughing, respiratory distress and marked weakness with an inability to stand. Although his body temperature was normal, he was cyanotic on exam with respiratory distress. His pulse ox was diminished at 85% although it did improve with oxygen therapy. Repeat bloodwork (CBC and chemistry panel) was completely within normal limits. Repeat thoracic radiographs did not show worsening of the pneumonia. The cyanosis was suspected to be due to respiratory muscle weakness and hypoventilation. “Koda” was hospitalized and provided with bilateral nasal cannulas for oxygen therapy. He was transitioned to intravenous antibiotics and IV fluid therapy. He was monitored closely for hypoventilation and the need for mechanical ventilation but responded well to just supplemental oxygen.

Within 24 hours, “Koda” was no longer oxygen dependent and he was starting to eat a bit on his own. He had difficulty swallowing the food and he was noted to regurgitate a small amount as well. He was still unable to stand or walk any distance without support. His degree of weakness did not seem to correlate with his pneumonia and an underlying neurologic condition was suspected. A complete neurologic evaluation was performed (see Table 1).

TABLE 1.NEUROLOGIC EXAMINATION

Personality/Mentation/Consciousness (Cerebrum/brain stem): alert but quietHead posture/Coordination (Vestibulo-cerebellar): normalMusculoskeletal description: generalized muscle wasting; oral exam had thick, ropy saliva in both commissures and hanging from mouth

GAIT EVALUATION: (0:plegia; 1:unable to stand; 2:walks with support; 3:walks with falling; 4:walks without falling; 5:normal):

“Koda” has grade 1-2 tetraparesis; makes an effort to stand but is unable to without support. When supported, gait is characterized by very short, choppy tight movements with limbs partially flexed (walking on pointed toes instead of fully plantigrade/palmigrade).

CRANIAL NERVE EXAM (0=absent; 1=decreased; 2=normal):

LIMB EVALUTION (0=absent; 1=decreased; 2=normal; 3=increased, 4=clonus):

SACRAL EVALUATION:Anal tone/bladder function: indwelling urinary catheter in place – unable to assess

SENSORY EXAMINATION:Sensory Deficits (nociception): normalSensory Level (panniculus): diffusely reducedHyperpathia: none

NEUROLOCALIZATION:1) Diffuse neuromuscular vs 2) caudal cervical / upper thoracic myelopathy

OS OD OS OD

Menace (2,7) 2 2 Facial sensation (5) 2 2

Pupil size (2,3,sym) = = Expressive muscles (7) 2 2

PLR (2,3): Direct 2 2 Palpebral reflex (5,7) 2 2

PLR (2,3): consensual 2 2 Retractor oculi (5,6) 2 2

Oculocephalic reflex (8,3,4,6) 2 2 Gag reflex 1 1

Ocular position (8,3,4,6) 2 2 Tongue (12) 2 2

Nystagmus none

Thoracic Limbs Pelvic Limbs

Proprioception 2 2 2 2

Hemihopping/hemistanding 0-1 0-1 0-1 0-1

Flex or Reflex 0 0 0-1 0-1

ECR Reflex 0 0 - -

Biceps Reflex 0 0 - -

Patellar Reflex - - 0-1 0-1

Cranial tibial Reflex - - 0-1 0-1

Crossed extensor Reflex 0 0 0 0

Based on “Koda’s” diffuse loss of reflexes, severe weakness and intact proprioception, dysphagia and regurgitation, a neuromuscular condition was considered most likely. Myasthenia gravis was considered a top differential given his at-risk breed (Akita) and the very acute onset/rapid progression and coinciding aspiration pneumonia. Although no megaesophagus had been noted on radiographs, frequent recheck assessment was warranted as changes occur rapidly in the fulminating form of this disease. A post-vaccinal acute polyradiculoneuritis (see Table 2) was also considered a top differential. Additionally, metabolic conditions related to diffuse muscle weakness and regurgitation such as Addison’s disease and hypothyroidism were considered possibilities for “Koda”. Esophagitis, underlying neoplasia with secondary myopathy/neuropathy were also considered differentials. While a caudal cervical or upper thoracic spinal cord condition was considered possible, it was felt “Koda” would have far more proprioceptive deficits noted – especially in his pelvic limbs. However, if a complete workup for neuromuscular disease failed to reveal a diagnosis or he was not improving, further workup for C6-T2 myelopathy to include MRI would be considered.

“KODA’S” DIAGNOSTIC WORKUP The diagnostic tests in Table 3 were recommended to rule out the differentials as outlined above.

DIAGNOSISMyasthenia Gravis

DISCUSSION Detailed discussions of neuromuscular disease and myasthenia gravis are beyond the scope of this article and the reader is referred to the listed references.

Myasthenia GravisDefinition and EtiologyMyasthenia gravis (MG) is an immune-mediated disorder of the neuromuscular junction. It results from autoantibody-mediated destruction of acetylcholine (ACh) receptors of the neuromuscular junction which results in

TABLE 2.ACUTE POLYRADICULONEURITIS

Definition• An acquired peripheral neuropathy involving segmental demyelination

and degeneration of axons and myelin of the ventral nerve roots.• The most common canine peripheral neuropathy!

Neurologic Exam Findings

• Causes an acute, ascending flaccid LMN tetraparesis/paralysis – signs begin in pelvic limbs and ascend to involve front limbs, neck and head.

• Often starts with stiff, stilted gait, followed by ataxia, progressing to marked weakness and then paralysis within 48 hours.

• Peripheral reflexes are decreased or absent, muscle tone is decreased. • Severity peaks in about 10 days.

Types

• Coonhound paralysis (CHP): immune-mediated reaction to an antigen in the saliva of raccoons. Neurologic signs develop 7-14 days after exposure

• Idiopathic: identical to CHP but no known exposure to raccoons. Possible etiologic agents: Campylobacter, Toxoplasma, other infectious agents

• Post-vaccination: identical to CHP but temporal relationship to vaccination has been reported

Treatment • Supportive only, nursing care

Prognosis

• Most affected dogs begin to spontaneously improve within 3 weeks with complete recovery by 2-4 months.

• Prolonged clinical signs (up to 6 months), incomplete recovery and lack of improvement have all been reported

• Recurrence (unless raccoon related) is rare

TABLE 3.DIAGNOSTIC TESTS

Abdominal Ultrasound Bilateral chronic nephropathy with nephrocalcinosis. Otherwise unremarkable.

Thyroid PanelT4 (reference range: 1.0-4.0 ug/dL)Free T4 (reference range: 0.6-3.7 ng/dL)TSH (reference range: 0.05-0.42 ng/mL)

NormalT4 = 1.4 ug/dL

Free T4 = 1.2 ng/dLTSH = 0.07 ng/mL

Cortisol (reference range: 2.0-6.0 ug/dL) 6.7

Neospora IFA Negative

Toxoplasma IgM and IgG Negative

Tick PCR Panel (Anaplasma, Babesia, Bartonella, Canine Hemotropic Mycoplasma, Ehrlichia, Hepatozoon, Leishmania, Neorickettsia risticii, Rocky Mountain spotted fever)

Negative

ACh-Receptor Antibody Reference range: <0.6 nmol/L: normal >0.6 nmol/L: positive and diagnostic of

acquired myasthenia gravis

Positive at 4.23 nmol/L

decreased numbers of functional receptors. Sensitivity of the post-synaptic membrane to acetylcholine is reduced, therefore, fewer action potentials are conveyed which results in a decreased muscular response. Clinically this manifests as decreased strength of striated muscles with resultant paresis or paralysis of the muscles of the limbs, eyes, face, esophagus and oropharyngeal areas.

Acquired MG is an immune-mediated disease and as in many immune diseases, the inciting cause is often unknown. One theory is that autosensitization against ACh receptors occurs within the thymus as the thymus appears to be important in teaching T lymphocytes to recognize “self” from “non-self.” Clinical Note: Dogs who develop neoplasia in the thymus gland (thymoma) may have MG as a paraneoplastic syndrome. Approximately 3% of dogs with MG have a cranial mediastinal mass. Another theory is that exposure to viral or bacterial antigens mimic self-antigens (such as the ACh receptor) and stimulates the immune system to attack.

Any breed may be affected by MG; however, the Akita, German Shorthaired Pointer, Chihuahua, Scottish Terrier, German Shepherd Dog, Newfoundland and Great Dane are particularly at-risk breeds.

Acquired MG may be associated with other immune-mediated disorders such as hypothyroidism, polymyositis, masticatory muscle myositis, and hypoadrenocorticism. Estrus and pregnancy may exacerbate active MG in intact female dogs. Vaccination may exacerbate active MG – as was suspected in “Koda.” Clinical Note: “Koda” was likely experiencing mild active MG (and hence the drooling, dysphagia and mild progressive weakness the owner had been noticing at home) when he received his 3 vaccinations. Within 5 days he had progressed to an acute, fulminating case of MG with hypoventilation, hypoxemia, non-ambulatory tetraparesis in addition to worsened oropharyngeal weakness.

Forms of MGThere are 3 forms of MG – generalized, focal and acute fulminating.

The generalized form is the classic form of MG characterized by limb weakness exacerbated by exercise and improved by rest. Clinical Note: Neurological evaluation in a generalized MG

patient may be completely normal if the dog has been at rest. Pelvic limbs are often more clinically affected than thoracic limbs. The gait is often stiff and choppy and a hunched “roach back” posture is common after activity. Affected dogs often develop a progressively shorter stilted stride, followed by sitting or lying down or a reluctance/inability to walk. There is usually no ataxia and proprioceptive testing is within normal limits. Postural reactions, segmental spinal reflexes, muscle mass and tone are all often normal, however, when a patient is fatigued, tendon reflexes are often markedly diminished to absent. Esophageal dysfunction is very common as the canine esophagus contains a high proportion of skeletal muscle.

Focal MG is characterized by focal involvement of the muscles of the head and neck. Affected dogs often exhibit excessive salivation with ropy saliva due to facial muscle weakness; significant dysphagia characterized by multiple ineffective attempts to swallow food due to oropharyngeal weakness; a high-pitched or absent bark (dysphonia) due to laryngeal weakness; regurgitation due to esophageal weakness/megaesophagus; and sometimes weak eyelid movements. Clinical Note: Focal signs may be present without evidence of generalized limb weakness.

The acute fulminating form of MG is fortunately a rare form of MG that results in rapidly progressive non-ambulatory tetraparesis with or without signs of esophageal or pharyngeal dysfunction. Hypoventilation and death can occur due to respiratory muscle weakness/failure. Spinal reflexes are depressed or absent. This form of MG mimics diseases that cause acute onset lower motor neuron tetraplegia such as tick paralysis, acute polyradiculoneuritis (see Table 2), snake envenomation, botulism, etc.

DiagnosisThe diagnosis of MG is made by demonstrating a positive serum antibody titer to acetylcholine receptors in a patient with appropriate clinical signs. This assay detects about 98% of dogs with generalized acquired MG, however, titers may be negative early in the disease. Clinical Note: ACh receptor antibodies are also elevated in some dogs with focal MG, however, seronegative MG is more common in this group. If a seronegative result is obtained in a dog with highly suggestive clinical signs (and clinical response to therapy), a repeat of the ACh

receptor antibody titer should be considered in one month.

An ACh receptor antibody greater than 0.6 nmol/L is considered positive in the dog. There is no correlation between the clinical severity of MG and the level of the ACh receptor antibody level. There is only one lab in the country performing ACh receptor antibody testing – the Comparative Neuromuscular Lab in California. The turnaround time for this test is long and can be up to two weeks. It is often necessary to begin presumptive therapy for these dogs while pending results of the test otherwise significant decline in patient condition is likely.

Electrodiagnostic testing can be helpful in differentiating MG from other forms of neuromuscular weakness. Unlike most peripheral neuropathies and myopathies, EMG and NCV tests are usually normal in MG patients. Unlike tick paralysis or cases of intoxication, the evoked CMAP is normal in MG patients. Tensilon testing, using edrophonium as a quick acting intravenous anticholinesterase drug to improve neuromuscular transmission, was historically available but is no longer clinically available.

Treatment and MonitoringAn important part of treatment for MG is nursing and supportive care. Recumbent animals need to be kept on adequate padded bedding and should be turned frequently. Passive range-of-motion exercises should be performed to maintain muscle and joint integrity. Access to food and water, and possibly parenteral fluid administration, may be required to maintain hydration. Dogs affected by megaesophagus should have elevated feedings – upright feeding position for 15 minutes using a Bailey chair – and a food format that is readily accepted by the dog. Placement of a temporary feeding gastrostomy tube may be beneficial in some animals until esophageal function improves.

Dogs with aspiration pneumonia should receive appropriate antibiotic therapy. Certain drugs, however, including aminoglycosides and ampicillin, should be avoided as they may cause neuromuscular blockade, inadvertently contributing to weakness and other clinical signs. H2 receptor antagonists or proton pump inhibitors should be considered to reduce gastric acidity to decrease damage associated with aspiration. In severely affected dogs with

acute, non-ambulatory tetraparesis, respiratory function must be closely monitored to determine a need for supplemental oxygen or mechanical ventilation.

Anticholinesterase drugs are the mainstay of therapy for acquired MG. These medications prolong the action of acetylcholine at the neuromuscular junction and serve to enhance neuromuscular transmission. Although MG is an immune-mediated disease, dogs often only require treatment with anticholinesterase medications in order to achieve clinical and immunologic remission. One study reported 47/53 dogs achieved remission (including a negative ACh receptor antibody titer) within an average of 6.4 months. The primary drug therapy is the long-acting anticholinesterase pyridostigmine bromide (Mestinon®). Neostigmine bromide can be used injectably until a patient can tolerate oral medications. Clinical Note: These medications have a narrow therapeutic index! It is important to start at the low end of the dose range and increase slowly if needed as some dogs are more sensitive to pyridostigmine than others and readily experience overdosage signs of drooling and increased regurgitation.

Although many patients can be successfully managed with anticholinesterase medications alone, acquired MG is an immune-mediated disease and some patients will require immunosuppressive therapy to achieve improvement or resolution of clinical signs. Immunosuppressive therapy is rarely used in the acute stages of diagnosis and particularly not when aspiration pneumonia is present. Commonly used medications include prednisone and azathioprine, although a whole host of therapies (including cyclosporine, mycophenolate mofetil, leflunomide, etc.) have been reported. Clinical Note: It is always debatable WHEN or even IF to start dogs with

MG on immunosuppressant medications. Caution is always advised when considering prednisone therapy as the expected polyuria/polydipsia may increase the risk of regurgitation. Additionally, prednisone therapy is capable of causing muscle weakness and muscle wasting which would be counter-productive in an MG patient.

Surgical removal of neoplastic thymic tissue is recommended in dogs affected by thymoma-associated MG.

The ACh receptor antibody titer should be evaluated every 3 to 6 months to determine if remission has occurred and whether treatment with anticholinesterase and/or immunosuppressive medications can be tapered and stopped. Clinical Note: Primary care veterinarians are encouraged to consult with local neurologists or internists experienced in treating myasthenia gravis for advice on individual patient management for the best possible patient outcome.

PrognosisThe prognosis for MG is variable. A substantial proportion of dogs (approximately 89%) with MG will experience spontaneous remission of their disease, although recurrences are possible. The most challenging part of therapy is the management of megaesophagus as it may not respond as readily to anticholinesterase or immunosuppressive therapies and it tends to lead to recurrent episodes of aspiration pneumonia. As such, dogs with MG with megaesophagus have a more guarded prognosis. The prognosis for the acute, fulminating form of MG is grave.

“KODA’S” TREATMENT At this time, all diagnostic tests for the evaluation of MG and acute

polyradiculoneuritis had not returned. As “Koda’s” condition was continuing to decline he was started empirically on pyridostigmine bromide (Mestinon®) orally at 30 mg PO q 12 hours for the presumptive treatment of myasthenia gravis. A low dosage was chosen with an option to increase based on his clinical response while pending his ACh-receptor antibody test result. Clinical Note: Careful dosing and adjustment of the dose of pyridostigmine is essential as it is an anticholinesterase drug (prolongs the action of acetylcholine at the neuromuscular junction to enhance neuromuscular transmission) and overdosage may result in classic SLUD syndrome (Salivation, Lacrimation, Urination, Defecation) and actually sometimes appear somewhat similar to presenting signs of myasthenia gravis.

Within two to three hours of receiving his first dosage of pyridostigmine, “Koda” was actually able to stand up and took a few steps! He began to eat more readily and did not experience further regurgitation. His pyridostigmine was continued and “Koda” improved daily and was discharged from the hospital. His ACh receptor antibody test returned the following week at 4.23 nmol/L which was strongly positive for myasthenia gravis.

As “Koda” is having a marked positive clinical improvement and still recovering from aspiration pneumonia, further therapy with immunosuppressives is not being considered at this point. “Koda” will continue to be monitored every 3-6 months with an ACh receptor antibody titer to monitor for remission and determine when/if treatment with pyridostigmine can be stopped. If his titer shows no signs of abating or he declines clinically, consideration may be given to additional immunosuppressant therapy when his aspiration pneumonia is fully resolved.

REFERENCESMariani, Christopher L, Neuromuscular Junctional Disorders, Chapter 265. The Textbook of Veterinary Internal Medicine, Ettinger and Feldman editors, 7th edition, Elsevier, St. Louis, 2018.

Mariani, Christoper L, Peripheral Nerve Disorders (Acute Polyradiculoneuritis), Chapter 263. The Textbook of Veterinary Internal Medicine, Ettinger and Feldman editors, 7th edition, Elsevier, St. Louis, 2018.

CLINICAL ASSESSMENT

1 What IS NOT a classic neurologic finding with neuromuscular disease?

a. LMN paresis/paralysisb. Diminished or absent spinal reflexesc. Diminished or absent proprioceptiond. Weakness of head/neck muscles

2 Which of the following will present most differently upon examination?

a. Myasthenia gravisb. IVDD at C4-C5c. Addison’s diseased. Acute polyradiculoneuritis

3 Which of the following breeds is not at-risk for MG?

a. Dalmatianb. Newfoundlandc. Akitad. German Shorthaired Pointer

4 Focal MG is characterized by which of the following:

a. Droolingb. Dysphonia (change in bark)c. Dysphagia (difficulty eating/swallowing)d. Regurgitatione. All of the above

5 Dogs with focal MG usually have limb weakness also. True or False?

6 Dogs with focal MG may have negative ACh receptor antibody tests. True or False?

7 Higher ACh receptor antibody levels correlate with MG disease severity. True

or False?

8 MG is an immune-mediated disease. The mainstay of MG therapy is simultaneous

use of long-acting anticholinesterase and immunosuppressant medications. True or False?

9 Spontaneous remission is very common with MG. True or False?

10 The long-acting anticholinesterase medications have a wide margin of safety

and dosing should start relatively aggressively, especially with a dog in an acute, fulminating MG crisis. True or False?

1. C. Diminished or absent proprioception.

2. B. IVDD at C4-C5. This would cause a caudal cervical myelopathy with more pronounced weakness in the pelvic limbs but with more CP deficits expected. Hyperpathia at C4-C5 could also be expected. The remainder of the differentials can cause diffuse muscle weakness and regurgitation.

3. A. Dalmatian. Although any breed may be affected by MG, the Akita, German Shorthaired Pointer, Chihuahua, Scottish Terrier, German Shepherd Dog, Newfoundland and Great Dane are particularly at-risk breeds.

4. E. All of the above. Focal MG is characterized by focal involvement of the muscles of the head and neck. Affected dogs often exhibit excessive salivation with ropy saliva due to facial muscle weakness; significant dysphagia characterized by multiple ineffective attempts to swallow food due to oropharyngeal weakness; a high-pitched or absent bark (dysphonia) due to laryngeal weakness; regurgitation due to esophageal weakness/megaesophagus; and sometimes weak eyelid movements.

5. False. Focal MG may be present without evidence of generalized limb weakness.

6. True. The diagnosis of MG is made by demonstrating a positive serum antibody titer to acetylcholine receptors in a patient with appropriate clinical signs. This assay detects about 98% of dogs with generalized acquired MG, however, seronegative results are more common in dogs with focal MG.

7. False. There is no correlation between the clinical severity of MG and the level of the ACh receptor antibody titer. Titers do appear to correlate well with clinical disease monitoring for a single individual, therefore, should be serially monitored and used to gauge disease remission with potential discontinuation of medications when noted.

8. False. Anticholinesterase drugs are the mainstay of therapy for acquired MG. These medications prolong the action of acetylcholine at the neuromuscular junction and serve to enhance neuromuscular transmission. Although MG is an immune-mediated disease, dogs often only require treatment with anticholinesterase medications in order to achieve clinical and immunologic remission.

9. True. A substantial proportion of dogs (approximately 89%) with MG will experience spontaneous remission of their disease, although recurrences are possible.

10. False. The long-acting anticholinesterase medications have a very narrow safety margin. It is important to start at the low end of the dose range and increase slowly if needed as some dogs are more sensitive to pyridostigmine than others and readily experience overdosage signs (classic SLUD syndrome - salivation, lacrimation, urination, defecation). It can be confusing as overdosage signs actually sometimes appear somewhat similar to presenting signs of myasthenia gravis.

CLINICAL ASSESSMENT ANSWERS: